Brightfocus Foundation

“A draft of the federal form 990 is distributed to the audit committee for review prior to being submitted to the internal revenue service. The draft federal form 990 is distributed early enough to provide each committee member with a reasonable amount of time for review and submission of questions or comments prior to the filing deadline. The final federal form 990 is distributed to each member of the full board of directors prior to being filed with the internal revenue service. The draft or final federal form 990 may be distributed in person, by regular mail, e-mail, or fax.”

“Brightfocus has all employees, officers, and directors agree to the code of conduct that includes adherence to the conflict of interest and implementation policy. Each board director, officer, and employee is required to complete a conflict of interest disclosure statement annually. Employees meet annually with the brightfocus' chief compliance officer to review their conflict of interest statements, and give an annual conflict of interest compliance report to the board chair and vice chair. If a conflict is reported, it is then referred to the president/ceo and/or brightfocus' legal counsel and, if appropriate and necessary, then to the board of directors or its appointed committee for further action. The director's and officer's statements are reviewed by the brightfocus legal counsel. If a conflict is reported, it is then referred to the board of directors or its appointed committee for further action. At the time of the brightfocus discussion and decision concerning a conflict of interest, the conflicted party is not present in the meeting.”

“Brightfocus' board of directors has overall authority and responsibility for approving the annual budget which includes salary and benefits for all employees at every level including non-director officers and key employees. All pay adjustments are made on a yearly basis effective april 1st, the beginning of the brightfocus fiscal year. Before approving the compensation of the president/ceo, the board determines the total compensation to be provided by brightfocus to the president/ceo is reasonable in light of the position, responsibility and qualification of the position held including the result of an evaluation of prior performance for brightfocus, if applicable. The president/ceo is evaluated annually by the board of directors through the use of an in-depth goal attainment structure, (developed with advice from board source) that includes a self assessment and a board of directors assessment and evaluation against set goals, outcomes and deliverables. In addition, the board of directors periodically engages an outside consultant to obtain and consider appropriate data, including a salary survey, which includes information compiled from the federal form 990 of other organizations, concerning compensation paid to ceos in like circumstances. In making the determination, the board of directors shall consider total compensation to include the salary and value of all benefits provided by brightfocus to the individual in payment for services. At the time of the brightfocus board discussion and decision concerning the president/ceo's compensation, the president/ceo is not present in the meeting. The board shall set forth the basis for its decisions with respect to compensation in the minutes of the meeting at which the decisions are made, including the conclusions of the evaluation and the basis for determining that the individual's compensation was reasonable in light of the evaluation and comparability data. The president/ceo is charged with the setting of salaries of all other employees in accordance with a compensation structure and budget approved by the board of directors. The president/ceo and human resources review employee compensation and benefits that include key employees, by periodically engaging an outside consultant to conduct compensation and benefit benchmarking studies that include various regional and national non-profit compensation reports and surveys. Compensation deliberations and decisions include the review of self and supervisory evaluations of employee performance compared to set individual and organizational goals.”

“Brightfocus makes its governing documents including its articles of incorporation and bylaws, the federal form 1023, the 501(c)(3) letter of determination from the internal revenue service, conflict of interest policy, audited financial statements and federal form 990 available to the public upon request. In addition, the public also has access to the annual report, audited financial statements, the 501(c)(3) letter of determination from the internal revenue service, and federal form 990 on our website.”

“Brightfocus funds exceptional scientific research worldwide to defeat alzheimer's disease, macular degeneration, and glaucoma and provides expert information on these heartbreaking diseases. Our vision is: a world free from diseases of mind and sight. Collectively, 1 in 16 people over the age of 40 in the u.s. Has one of these diseases. Brightfocus has a proven track record of supporting the most innovative, early-stage research seeking better understanding, treatments, or, ultimately, a cure for these diseases. Since 1973, brightfocus has awarded nearly $250 million in research grants to thousands of scientists around the world. Our research funding has led to major contributions to the understanding of these diseases and support for scientists who have received prestigious awards, including two nobel prizes. An indicator of our ability to push new boundaries of knowledge is that brightfocus-supported research was recently found to have had twice the impact on driving future science than work supported by many other organizations. The world-class research identified and supported by brightfocus is on the cutting-edge of the fight to save mind and sight. Our funding acts as a catalyst in early-stage research. The brightfocus research programs are designed to provide initial funding for highly innovative experimental ideas. Due to the structured grant review and approval process, the research impact of brightfocus is very high. Most recipients of brightfocus funding go on to receive future grants from other sources that are up to 10 times larger than the original brightfocus award. This high return on brightfocus investment speaks to our ability to identify promising research in its earliest stages and spawn future scientific discoveries. It is our firm belief that having the courage to invest in innovative ideas will lead to revolutionary approaches and life-saving breakthroughs. Along with funding cutting-edge research to find cures to some of the world's costliest diseases, brightfocus also provides free educational materials and support to hundreds of thousands of those impacted by these diseases nationwide. We root these educational materials in the latest research findings. Brightfocus increases public awareness of alzheimer's, macular degeneration, and glaucoma, and communicates with thought leaders and elected officials about the importance of scientific research in these areas. Brightfocus' award-winning public service announcements (psa) have appeared on television, radio, and in print throughout the nation. The impact of alzheimer's. Make a plan today: get your eyes checked and now is the moment to stop alzheimer's disease powerfully seek to raise awareness and early detection, and similar messages have been delivered through donated print psa space in airports and train stations, as well as at pharmacies, supermarkets and digitally. In fiscal year 2021, these psa messages generated $10,280,294 in donated media services and garnered over 592 million impressions. Since 2014, the brightfocus chats have brought together patients and caregivers for free, interactive monthly telephone forums to learn from, and ask questions of, leading researchers and specialists on vision diseases. The chats are archived on our web site, with audio and print transcripts available in a number of accessible formats. We continue to increase our print publications, many in spanish, that provide helpful information to patients and caregivers, and regularly unveil new video and audio resources in conjunction with allies in the medical and scientific communities. Partnering with several high-profile public and private organizations, brightfocus is helping better educate the public on the importance of participation in clinical research as a way to accelerate the path to cures for neurodegenerative diseases. Specifically, brightfocus is a presentation partner for turning point, a documentary on the scientists and clinical trial volunteers workin”

“Alzheimer's disease research (adr) - alzheimer's disease is the only cause of death among the top 10 in america without a way to prevent, cure, or even slow its progression. It is an irreversible degeneration of the brain that causes disruptions in memory, cognition, personality, and other functions and inevitably leads to death. An estimated 5.5 million americans have alzheimer's disease, about two-thirds are women. Brightfocus' adr program funds research focused on understanding the causes of alzheimer's disease, its early detection, and treatments to help slow or stop its progression, and ultimately to prevent the disease altogether. Adr annually awards peer-reviewed grants to scientists from institutions worldwide who are conducting biomedical and clinical research on alzheimer's disease. Since inception, brightfocus has contributed more than $154 million to the conquering of alzheimer's disease. During the fiscal year ended march 31, 2021, adr awarded $11,650,745 in peer-reviewed grant awards to 46 new research projects and thirteen other scientific awards to make a total of $14,187,967 in funding. Notable projects include: using the eye to detect dementia; lifestyle effects on risk of alzheimer's (including lipids); drug discovery; molecular and digital biomarkers; the role of inflammation and vascular health in disease risk; role of sleep disturbances causing increased risk of cognitive issues; modeling alzheimer's in a dish; and better use of modern technologies, including mobile technologies, big data, and systems genetics analysis for increased and decreased risks. Additional information about specific projects is included in schedules f & i. Brightfocus is honored to have supported the early research of two nobel prize winners: dr. Stanley prusiner and dr. Paul greengard, whose work has been instrumental to our current understanding of alzheimer's disease. Brightfocus continues its partnership with the academic journal "molecular neurodegeneration" as the official journal of the brightfocus foundation. The journal publishes technical papers related to neurodegeneration in the three disease areas. To accelerate scientific progress, it is an "open access" journal, and all content is free of charge. This open access ensures maximal reach of journal contents to scientists and care providers worldwide. Molecular neurodegeneration is currently the highest impact open access journal in the neurosciences. In addition to supporting cutting-edge research, alzheimer's disease research provides excellent resources on detecting, treating, and living with the disease. These are available in both print as well as on our website, www.brightfocus.org.”

“Macular degeneration research (mdr) - age-related macular degeneration is a leading cause of vision loss in the united states. It destroys the macula, the part of the eye that provides sharp, central vision needed for seeing objects clearly. The most common eye condition in people age 60 and older, it can lead to vision loss in one or both eyes, making it difficult to recognize faces, drive a car, or read. As many as 11 million americans have some type of macular degeneration, including both the early and later stages of the wet and dry types. This number is expected to double to nearly 22 million by 2050. Macular degeneration research (mdr), a program of brightfocus, has awarded more than $39 million to scientists studying the disease. The latest research is focused on novel treatments for the disease, understanding its causes and progression, prediction methods and disease modeling, drug therapies, the role of the metabolism in disease risk, genes, the role of the immune response in disease risk, and new screening techniques. Mdr grants are available to macular degeneration researchers worldwide. Mdr places special emphasis on encouraging applications from young scientists and those with cutting-edge ideas. Annual grant applications are peer-reviewed, and recipient selections are based on scientific merit. During the fiscal year ending march 31, 2021, mdr awarded $6,135,716 in peer-reviewed grant awards to 20 new research projects, with 3 additional scientific projects that take the total funding to $6,175,716. Details about specific projects are included in schedules f & i. In addition to supporting cutting-edge research, macular degeneration research provides excellent resources on detecting, treating, and living with this disease. These are available in both print as well as on our website, www.brightfocus.org.”

“National glaucoma research (ngr) - glaucoma is the second leading cause of blindness worldwide affecting approximately 80 million people according to the world health organization. More than three million americans have glaucoma and it is estimated that only half of the people living with the disease are aware they have it. In the united states, glaucoma is a leading cause of blindness among black and hispanic americans. With early detection and treatment, glaucoma often can be managed to protect eyes from more serious vision loss. Brightfocus' ngr program has awarded more than $43 million worldwide for the study of glaucoma. Ngr-supported research has been focused on the eye-brain connection, the biomechanics for pressure buildup in the eye, optic nerve regeneration, discovering glaucoma risk genes, ai/deep learning, sleep disturbance and risk of developing glaucoma, and developing early glaucoma screening and targeted treatments, amongst other innovative pursuits. Ngr grants are available to glaucoma researchers worldwide. Ngr places special emphasis on encouraging applications from young scientists and those with cutting-edge ideas. Annual grant applications are peer-reviewed, and recipient selections are based on scientific merit. During the fiscal year ending march 31, 2021, ngr awarded $3,097,742 in peer-reviewed grant awards for 17 new projects and seven other scientific awards to make a total of $4,892,686 in funding. Details about specific projects are included in schedules f & i. In addition to supporting cutting-edge research, national glaucoma research provides excellent resources on detecting, treating, and living with the disease. These are available in both print as well as on our website, www.brightfocus.org.”

“Recoveries of prior year grants 518,962. Change in present value of grants -7,225.”

“Region: europe (d) purpose of grant: alzheimer's disease research by whitney freeze, phd, entitled: (a2021007f) detecting leaky vessels in cerebral amyloid angiopathy - a novel approach. Investigators summary: this project combines state of the art magnetic resonance imaging techniques with detailed post-mortem examinations to explore associations between bbb leakage, subtle hemorrhagic brain pathology, and cognitive functioning in patients with cerebral amyloid angiopathy. The success of this project will ultimately provide the field with a new tool to predict risk of hemorrhages in dementia at an early stage, which will be pivotal in the selection of individuals for amyloid-modifying therapies, and for the development of new drugs to prevent the formation of bleeds. Grant awarded: $200,000, leiden university medical center - directoraat onderzoek, leiden, the netherlands. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021007f region: europe (d) purpose of grant: alzheimer's disease research by emil gustavsson, phd, entitled: (a2021009f) the landscape and expression of apoe transcripts in human brain and alzheimer's disease. Investigators summary: changes to the apoe rna molecule the template produced by dna that also translates into proteins, the building blocks in the body may contribute to the risk of alzheimer's disease (ad). The proposed project will use a new technology called long-read rna-sequencing to explore the different types of rna transcripts that are produced in ad. This will result in a full landscape of apoe rna transcripts to study their expression patterns in neurons and microglia and determine whether function correlates with disease using large, publicly available datasets. Grant awarded: $199,575, university college london, united kingdom. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021009f region: europe (d) purpose of grant: alzheimer's disease research by alexa pichet binette, phd, entitled: (a2021013f) characterization of tau pathology heterogeneity across the alzheimer's disease spectrum. Investigators summary: this study will use the latest positron emission tomography marker to image tau deposition in a large, longitudinal, well-characterized cohort ranging from pre-clinical older adults to people with dementia. Participants will be grouped according to their different tau subtypes and additionally characterized using biofluidic, genetic, and cognitive measurements to understand the mechanisms that underlie the accumulation of pathology and cognitive decline. Grant awarded: $200,000, lund university, department of clinical sciences, malmoe, sweden. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021013f region: europe (d) purpose of grant: alzheimer's disease research by maxime van egroo, phd, entitled: (a2021016f) the brainstem locus coeruleus: potential bridge between sleep-wake disruption and alzheimer's disease pathogenesis. Investigators summary: the proposed project postulates that a tiny region located deep in the brain, the brainstem locus coeruleus (lc), is particularly important for the link between sleep-wake disturbances and the earliest manifestations of alzheimer's disease (ad). Indeed, the lc is a crucial structure in the consolidation of the sleep-wake cycle and has been demonstrated to be among the first regions affected by ad. This research aims to use advanced brain imaging methods to extensively characterize the lc in healthy adults across the lifespan, in order to determine how modifications in the structure and function of the lc relate to changes in the sleep-wake cycle, in the accumulation of hallmark ad pathologies, and ultimately to cognitive decline. Grant awarded: $200,000, maastricht university, maastricht, the netherlands. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021016f region: east asia & pacific (d) purpose of grant: alzhei”

“Region: europe (d) purpose of grant: alzheimer's disease research by henne holstege, phd, entitled: (a2021031s) blood-based markers for alzheimer's pathology in cognitively healthy centenarians: revealing mechanisms of resistance and resilience. Investigators summary: this proposal will investigate to what extent centenarians can tolerate high levels of alzheimer related proteins in their brains (resilience) and to what extent centenarians escape the accumulation of these alzheimer related proteins (resistance). State of the art technology will be used to measure proteins in the blood of 400 cognitively healthy centenarians and their family members to determine whether centenarians use different protective mechanisms to maintain brain function. This research can help identify lifestyle and genetic factors that influence resilience and resistance. Grant awarded: $299,707, vu university medical center amsterdam, the netherlands. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021031s region: europe (d) purpose of grant: alzheimer's disease research by soyon hong, phd, entitled: (a2021032s) immune mechanisms of synapse loss in alzheimer's disease. Investigators summary: recent single-cell profiling studies have shown that certain 'activated' microglia surround amyloid plaques in alzheimer's disease (ad) brains and express a unique set of genes, hence coined 'disease-associated macrophages' (dams). What dams do and whether dams are beneficial or detrimental are not known. Pilot data suggest that dam-like cells are expressed early in ad models when synapses are vulnerable to loss. This proposal will test the hypothesis that dams facilitate synapse loss in ad via upregulation of spp1 (osteopontin) and, determine whether this is complement dependent, using in vivo mouse and in vitro models as well as human ad brains. Grant awarded: $300,000, university college london, united kingdom. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021032s region: europe (d) purpose of grant: alzheimer's disease research by renzo mancuso, phd, entitled: (a2021034s) from genetics to the cellular phase of alzheimer's disease: untangling the role of lipid pathways in microglia responses to amyloid pathology. Investigators summary: genetic studies reveal a link between neuroinflammation and susceptibility for alzheimer's disease (ad), suggesting that inflammation might be a driver of the disease opposed to just a consequence. This project aims to determine the link between ad genetic risk, microglia, and lipid metabolism by combining novel models where human stem cell derived microglia are injected in ad mice, and single cell rna sequencing is used for in depth analysis of microglial function. By doing this, we will be able to dissect the contribution of microglia and lipid metabolism in the ad brain in a crucial human system. Grant awarded: $199,568, vibvzw, gent, belgium. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021034s region: europe (d) purpose of grant: alzheimer's disease research by jonas neher, phd, entitled: (a2021035s) the role of hif-1a in the microglial response to alzheimer's disease pathology. Investigators summary: one role of microglia is to shield the brain from the damaging effects of amyloid plaques this is called the microglial 'barrier function'. Importantly, genetic mutations that disrupt this microglial barrier lead to a strongly increased risk for developing alzheimer's disease (ad). Preliminary work identified a previously unknown molecular target whose genetic elimination significantly increases the microglial barrier around amyloid plaques. This project will characterize the long-term effects of manipulating this molecular pathway in two independent animal models of ad pathology, with a particular focus on molecular and functional changes in microglia, pathological hallmarks of ad and most importantly, cognitive function. Gr”

“Region: europe (d) purpose of grant: alzheimer's disease research by susanne wegmann, phd, entitled: (a2021044s) understanding tau-induced nuclear transport deficits in alzheimer's disease. Investigators summary: the aberrant interactions of tau with nucleopore proteins, nucleoporins (nups), induce a pronounced impairment in nucleocytoplasmic transport processes, whereby two mechanisms seem to play a role: direct binding of soluble tau to nups in pore complexes, and co-aggregation of nups with tau in cytosolic neurofibrillary tangles, the hallmark tau pathological change in alzheimer's brains. To understand how tau interacts with and impairs nuclear pores, the tau:nup interactome will be determined in human neurons and these findings will be correlated with the status of human ad brains. Cells equipped with a nuclear transport reporter will be used to screen for small molecules and genetic modifiers of tau-induced nuclear transport deficits. Grant awarded: $299,800, german center for neurodegenerative diseases, bonn, germany. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021044s region: north america (d) purpose of grant: alzheimer's disease research by cheryl wellington, phd, entitled: (a2021045s) the role of peripheral apoe in the high density lipoprotein fraction in vascular contributions to alzheimer's disease. Investigators summary: apoe is made both within the brain and outside the brain, but the "brain and "blood" pools of apoe are separated by the blood brain barrier. Circulating high-density lipoprotein (hdl) particles, or "good cholesterol", can help amyloid beta (ab) from getting stuck in the blood vessel wall as it moves from "brain" to "blood". Importantly, 6% of hdl also contains apoe, and these apoe-hdl particles seem to be the best at helping ab from getting stuck in the vessel. This project uses a new method to measure apoe-hdl in 2000 blood samples from people with dementia vs. People resistant to dementia and use additional test tube approaches to study how apoe-hdl acts on the small blood vessels of the brain. Grant awarded: $300,000, university of british columbia, vancouver, bc, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021045s region: north america (d) purpose of grant: alzheimer's disease research by sanjeev kumar, md, entitled: (a2018667s) identifying and targeting cortical inhibition deficits in agitation/aggression due to alzheimer's dementia. Emergency relief supplement due to covid-19. Grant awarded: $56836, centre for addiction and mental health, toronto, on, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2018667s region: europe (d) purpose of grant: alzheimer's disease research by dr. Marianne leger entitled: (ca2021013) lou rat as a model of cognitive resilience in the field of alzheimer's disease. Investigators summary: this project, which will take place at university of caen normandie, aims to understand the brain mechanisms responsible for this resistance to cognitive decline induced by alzheimer's disease.the identification of these neuroprotective mechanisms is unprecedented.it will therefore make it possible to develop innovative therapeutic strategies to increase the cognitive reserve of people with alzheimer's disease and thus resist the pathology. Grant awarded: $72,046, fondation vaincre alzheimer, paris, france. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2021013 region: europe (d) purpose of grant: national glaucoma research by ester reina-torres, phd, entitled: (g2021004f) mechanisms controlling aqueous humour segmental outflow in mice. Investigators summary: this project will contribute to understanding aqueous humour drainage better, which would help the development of more effective drugs to lower eye pressure and treat glaucoma. Grant awarded: $149,999, imperial college of science, technology and medicine, london, united”

“Region: east asia & pacific (d) purpose of grant: national glaucoma research by michael girard, phd, entitled: (g2021010s) the biomechanical phenotype of normal-tension glaucoma. Investigators summary: to understand why some patients with normal eye pressure develop glaucoma, this study proposes engineering and artificial intelligence tools to fully assess and understand the robustness of the optic nerve head (onh) in a given patient. Their goal is to establish whether onh robustness can help us predict who is at risk of developing future glaucoma damage, and if proven, we will be able to provide earlier treatment in the eyes that are deemed mechanically unstable. Grant awarded: $200,000, singapore eye research institute, singapore. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021010s region: europe (d) purpose of grant: national glaucoma research by pirro hysi, md, phd, entitled: (g2021011s) identification of potential glaucoma therapy targets through integrated machine learning analysis of multi-omic biomarkers. Investigators summary: the purpose of this project is to identify highly variable and modifiable molecular changes that participate in mechanisms causing primary open-angle glaucoma, as immediate targets of novel treatments. This project will identify modifiable changes of metabolism or chemical modifications of the dna that lead to glaucoma.this project will use powerful machine learning to stack millions of data points acquired through high-throughput platforms ("omics") in a very large number of individuals to identify robust signals of epigenetic and metabolic changes that together modulate the glaucoma risk. Grant awarded: $198,873, king's college london, united kingdom. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021011s region: north america (d) purpose of grant: national glaucoma research by michael reber, phd, entitled: (g2021014s) sensing elevated intra-ocular pressure in mouse models of glaucoma: potential role of piezos channels. Investigators summary: this study looks into a new set of pressure sensor molecules discovered in 2010 in mammals, the piezo1 and 2 receptors, expressed by retinal ganglion cells (rgcs) are sensing eye pressure. In this project, researchers want to investigate further the role of piezo1 and 2 receptors in sensing eye pressure in an animal model of glaucoma using pharmacological and genetic approaches and measure the effect on rgc death. Grant awarded: $200,000, university health network, toronto, on, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021014s region: east asia & pacific (d) purpose of grant: national glaucoma research by zhichao wu, phd, entitled: (g2021016s) accurate prediction and detection of glaucoma progression using hyperspectral and widefield optical coherence tomography imaging. Investigators summary: this project could provide the much-needed tools to better guide the decision making in glaucoma treatment. These tools can also be used to expedite the discovery of new treatments in glaucoma, by improving our ability to identify high-risk individuals to enroll in clinical trials and by providing sensitive outcome measures to detect treatment effects over a much shorter timeframe. Grant awarded: $199,504, centre for eye research australia limited, east melbourne, australia. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021016s region: europe (d) purpose of grant: national glaucoma research by darryl overby, phd, entitled: (cg2020003) selective targeting of schlemm's canal inner wall for next-generation glaucoma drugs: subpart c investigators summary: glaucoma is a blinding eye disease that can only be treated by lowering eye pressure. Our research has identified a particular cell type (schlemm's canal cells) that regulate eye pressure by controlling the drainage of aqueous humor from the eye. In this project, we wi”

“Region: north america (d) purpose of grant: macular degeneration research by brittany carr, phd, entitled: (m2021001f) tracking the development of reticular pseudodrusen and age-related retinal disease in prom1-null x. Laevis.. Investigators summary: this study involves characterizing a new animal model of age-related macular degeneration (amd) that will provide significant insight into the relationship between reticular pseudodrusen (rpd)and amd progression. Establishing rpd as an early-indicator of amd and understanding its role in amd progression will result in more effective prevention of amd-associated blindness. Grant awarded: $189,570, university of british columbia, vancouver, bc, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021001f region: north america (d) purpose of grant: macular degeneration research by rony chidiac, phd, entitled: (m2021003f) novel frizzled-4/lrp5 antibody-based agonist for neovascular macular degeneration. Investigators summary: for the first time, researchers of this study could precisely activate one receptor of the many mimicking wnt proteins and study its role in blood vessel formation and integrity. They aim to test this molecule's therapeutic potential in models mimicking the neovascular age-related macular degeneration (amd). These synthetic agonists are attractive therapeutic modalities to control the formation of new blood vessels during neovascular amd. Grant awarded: $200,000, university of toronto, on, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021003f region: middle east (d) purpose of grant: macular degeneration research by michelle grunin, phd, entitled: (m2021006f) integrated immunogenomics to develop translational treatment for age-related macular degeneration. Investigators summary: this study will use novel technological tools and diverse ancestry reference panels that were previously unavailable, to identify new genetic risk factors for age-related macular degeneration (amd) and possible new genetic or immune system targets for treatment of the disease. Researchers will utilize the existing genetics of the international amd genomics consortium, with over 50,000 samples, to investigate these issues on a large scale. Utilizing multiethnic participants will allow for discovery of rare genetic variants not previously investigated. Grant awarded: $200,000, hebrew university of jerusalem, israel. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021006f region: east asia & pacific (d) purpose of grant: macular degeneration research by yvette wooff, phd, entitled: (m2021012f) therapeutic replenishment of homeostatic microrna using extracellular vesicles for the treatment of age-related macular degeneration. Investigators summary: in the retina, extracellular vesicles (ev) are responsible for mediating this essential communication and work by delivering molecular cargo, including small gene regulators called microrna (mirna), to target cells and are reduced with degenerating retina. In this study, researchers will supplement the degenerating retina with essential retinal ev cargo derived from donor stem cells and investigate the effect on retinal health. Grant awarded: $198,062, the australian national university, canberra, australia. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021012f”

“Name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by moustafa algamal, phd, entitled: (a2021001f) restoring sleep and memory deficits in alzheimer's disease by targeting somatostatin interneurons. Investigator's summary: slow-wave sleep is closely associated with memory performance in healthy individuals and is also disrupted in alzheimer's disease. This project aims to find and activate the group of neurons responsible for slow-wave sleep regulation and improve their function in alzheimer's disease (ad) mouse models through two different approaches. The first approach will utilize a novel genetic technology to activate these neurons with light, followed by assessing memory and pathology of ad in animals. The second approach will rely on pharmacological approaches to support the function of these neurons. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021001f name of organization or government: brown university. (h) purpose of grant: alzheimer's disease research by benedetta assetta, phd, entitled: (a2021002f) astroglial inflammatory signaling in alzheimer's disease. Investigator's summary: neuroinflammation sits at the center of alzheimer's disease (ad) pathogenesis. This study will investigate the regulatory role of chi3l1, an inflammatory molecule that correlates with ad development. The biological mechanisms of chi3l1 in ad pathology will be studied using patient derived stem cells and animal models. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021002f name of organization or government: yale university. (h) purpose of grant: alzheimer's disease research by yifei cai, phd, entitled: (a2021003f) molecular mechanisms of axonal pathology in alzheimer's disease. Investigator's summary: amyloid deposits in alzheimer's disease are surrounded by axons with abnormally enlarged bulbous structures. These structures severely affect axonal conduction of signals and that this may be correlated with memory loss in humans. The goal of this project is to investigate the molecular and cellular mechanisms involved in the formation of these bulbs and determine if reversing this pathology is possible, and if so whether this can restore normal axonal function. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021003f name of organization or government: university of california, berkeley. (h) purpose of grant: alzheimer's disease research by xi chen, phd, entitled: (a2021004f) the relationship between amyloid/tau pathology and different memory processes underlying memory aging. Investigator's summary: the proposed project, focusing on early stage alzheimer's disease (ad), will examine the brain and behavioral deficits in older adults with normal cognitive performance but already harboring ad pathology. This study will use functional mri to investigate how different brain regions activate when participants view pictures of an object, a scene, and an object in a scene. Participants will complete a surprise memory test on the pictures 20 minutes later. These results will isolate brain activities that are critical for successful memory. Pet imaging will then be used to visualize the deposition of amyloid beta and tau in the brain to determine the specific effect these proteins have on different domains of memory performance (object, scene, and integrated object-scene memory) and what brain regions are most affected. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021004f name of organization or government: university of pennsylvania. (h) purpose of grant: alzheimer's disease research by april darling, phd, entitled: (a2021005f) engineering therapeutic trim11 disaggregases. Investigator's summary: a class of helpful proteins known as disaggregases have the ability to dissolve protein aggregates. One recently identified is trim11, an impressive protei”

“Name of organization or government: the jackson laboratory. (h) purpose of grant: alzheimer's disease research by niran hadad, phd, entitled: (a2021010f) systems genetics analysis of alzheimer's disease related sleep disruption. Investigator's summary: traditional mouse models of alzheimer's disease (ad) have provided substantial insights into possible mechanisms causing sleep loss in ad. However, these model lacks the genetic diversity required to identify genes conferring individual risk to develop ad-related sleep loss and subsequent cognitive decline. The work proposed here seeks to identify genes that underlie an individuals' risk for developing alzheimer's-related loss of sleep using a well-characterized, genetically diverse mouse model of ad that better models the complexity of human genetic diversity. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021010f name of organization or government: stanford university. (h) purpose of grant: alzheimer's disease research by harini iyer, phd, entitled: (a2021011f) lysosomal signaling in microglia and alzheimer's disease. Investigator's summary: microglia chew up dead cells and fight infections in the brain to make sure that other brain cells, such as neurons, function normally. When microglia eat bacteria or dead material, this material passes through the lysosome, where it gets recycled or broken up into smaller pieces. Dna mutations in people with alzheimer's disease occur in genes that are important for microglia and lysosome function. This project will investigate how these genes are important for the normal activity of microglia and lysosomes and how, over time, they can cause microglia to switch from being good for the brain to harming brain cells. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021011f name of organization or government: washington university school of medicine. (h) purpose of grant: alzheimer's disease research by karin meeker, phd, entitled: (a2021012f) tau phosphorylation in preclinical and symptomatic autosomal dominant alzheimer disease. Investigator's summary: changes in blood tau levels, cognitive tests, and brain network connectivity can be used as biomarkers to map disease progression and indicate conversion from preclinical to clinical alzheimer's disease (ad). It is unknown, however, how various phosphorylation sites on tau are associated with brain network organization and whether they contribute to the propagation of tau through brain networks. This study will use neuroimaging, cerebrospinal fluid, and cognitive markers to characterize and stage the temporal and spatial progression of tauopathy occurring during the transition period in autosomal dominant ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021012f name of organization or government: icahn school of medicine at mount sinai. (h) purpose of grant: alzheimer's disease research by anna podlesny-drabiniok, phd, entitled: (a2021014f) investigating the role of liver x receptors in control of alzheimer's disease risk genes and lipid clearance in hipsc-derived microglia. Investigator's summary: analysis of genetic factors contributing to alzheimer's disease (ad) point to the critical role of brain immune cells (microglia) and functions that they exert such as efficient removal of dying cells in the process called phagocytosis. In ad brains, immune cells are unable to properly remove amyloid plaques, and they sustain inflammation contributing to disease progression. This project will test whether liver x receptors and the ad risk gene, bhlhe40/41, are master regulators of microglial phagocytosis using human cells carrying ad mutations. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021014f name of organization or government: mayo clinic jacksonville. (h) purpose of grant: alzheimer's disease research by ana-caroline raulin, phd, entitled: (a2021015f) protec”

“Name of organization or government: j. David gladstone institutes. (h) purpose of grant: alzheimer's disease research by zhaoqi yan, phd, entitled: (a2021019f) fibrinogen-mediated innate immune activation and neuronal dysfunction in alzheimer's disease. Investigator's summary: fibrinogen, a blood coagulation protein, deposits in the brains of people with alzheimer's disease (ad) and causes microglia activation, oxidative stress, neuronal loss, and cognitive impairment. This proposal will use a multi-pronged experimental design to examine the cerebrovascular mechanisms regulating neuronal dysfunction in ad. State-of-the-art imaging will be used to study the interaction of fibrinogen and neurons in living mice with subcellular resolution. The transcriptional machinery underlying fibrinogen-mediated oxidative stress will be determined and used to generate a global transcriptional atlas in the brain of ad mice at single-cell level. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021019f name of organization or government: university of california, san francisco. (h) purpose of grant: alzheimer's disease research by beika zhu, phd, entitled: (a2021020f) characterizing the role of microglial gpr56 in alzheimer's disease. Investigator's summary: this proposal will test the hypothesis that microglial gpr56, a cell surface protein that receives signals from neighboring cells, plays a role in maintaining brain function and stops alzheimer's disease (ad) progression. Cpr56 function will be determined by generating a new mouse model where cpr56 activity is inhibted, or knocked down. Investigating changes in inflammatory responses, memory, and motor function, will elucidate the mechanisms by which gpr56 mediates ad onset and progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021020f name of organization or government: icahn school of medicine at mount sinai. (h) purpose of grant: alzheimer's disease research by kathryn bowles, phd, entitled: (a2021021s) single cell profiling of mapt splicing mutation ipsc-derived organoids and brain tissue. Investigator's summary: progressive supranuclear palsy (psp) and frontotemporal dementia (ftd) are age-related dementias associated with the accumulation of 4r tau. Psp and ftd can be caused by specific mutations on the gene encoding for tau, mapt. A panel of ipsc lines that carry specific psp/ftd mutations and have increased 4r tau expression, will be used to generate 3d brain organoids. Gene expression analyses and phenotypic assays will be conducted to identify early changes associated with 4r tau and the development of disease. Next, bulk and single-nuclei sequencing will be carried out on brain tissues from individuals with the same mapt mutations to validate these changes and thoroughly characterize the impact of 4r tau accumulation in adult human brain. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021021s name of organization or government: brigham and women's hospital, inc. (h) purpose of grant: alzheimer's disease research by oleg butovsky, phd, entitled: (a2021022s) apoe4 gender-dependent regulation of neutrophil-microglia crass-talk in alzheimer's disease. Investigator's summary: apoe plays a critical role in inducing microglial phentoypes that are associated with neurodegeneration. A key question is whether apoe variants derived from innate immunity peripheral cells (macrophages and neutrophils) also control immune responses driven by microglia and contribute to disease progression. Preliminary data show that human apoe variants mediate differential regulation of pro-inflammatory signatures in neutrophils in a sex-dependent manner. Importantly, recent studies identified similar inflammatory signatures in blood neutrophils, which was associated with cognitive decline in alzheimer's disease (ad) patients. This proposal aims to investigate the role of apoe variants in the regulation o”

“Name of organization or government: ohio state university. (h) purpose of grant: alzheimer's disease research by jie gao, phd, entitled: (a2021028s) targeting e3 ligase idol to mitigate apoe4-mediated tau pathology. Investigator's summary: apolipoprotein e4 (apoe4) markedly exacerbates tau pathology and tau-mediated neurodegeneration in alzheimer's disease (ad). Therefore, targeting apoe4's detrimental effects in tau pathology might serve as a promising strategy for the treatment of ad. Idol is a novel, major regulator of brain apoe receptor expression, and has a profound impact on apoe metabolism. This study aims to understand the multifactorial role and underlying mechanisms of action of idol in mitigating apoe4-mediated tau pathology in ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021028s name of organization or government: university of california, san francisco. (h) purpose of grant: alzheimer's disease research by jason gestwicki, phd, entitled: (a2021029s) de-phosphorylation of tau by chaperone complexes. Investigator's summary: tau is abnormally modified by phosphorylation and phosphorylation at specific sites may precede disease. While the enzymes that add phosphorylation groups are well known, there has been significantly less attention paid to the enzymes, termed phosphatases, that remove these modifications. Exciting preliminary results showed that specific 'helper' proteins, or chaperones, can bind to tau and recruit a specific phosphatase, pp5. This study will use cutting edge techniques to look at protein structures and interactions of chaperones with pp5 to determine whether these interactions are important for removing phosphorylation groups from tau. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021029s name of organization or government: columbia university. (h) purpose of grant: alzheimer's disease research by ulrich hengst, phd, entitled: (a2021030s) transcriptional dysregulation of the endocytic machinery in ad. Investigator's summary: endosomes form complexes with multiple other proteins, including transferrins (tf), to perform intracellular sorting of substances that will ultimately be degraded or recycled. A new tf complex that is associated with amyloid has been identified and is proposed to transcriptionally regulate components of the retromer, a multiprotein complex that mediates the sorting and transport of proteins out of early endosomes. This project will determine the sufficiency of the tf complex to deregulate the expression of retromer components and to cause endosomal trafficking defects, and investigate whether ad pathology is altered in mice lacking one of the tfs. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021030s name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by laura ibanez, phd, entitled: (a2021033s) pathophysiology of srnas in alzheimer's disease. Investigator's summary: this proposal will characterize the different populations of small rnas in brain, plasma, and cerebrospinal fluid of individuals with alzheimer's disease. Their biological role will be investigated by: i) identifying which small rnas are different between cases and controls in each specimen (brain, plasma and cerebrospinal fluid); ii) use small rnas to generate tools that allow disease prediction, and iii) use cellular models to investigate the biological consequences of dysregulating the identified small rnas. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021033s name of organization or government: northeast ohio medical university. (h) purpose of grant: alzheimer's disease research by erin reed-geaghan, phd, entitled: (a2021036s) developmental determinants of sexually divergent neuroinflammatory processes in alzheimer's disease. Investigator's summary: in addition to the pathological hallmarks of amyloid plaqu”

“Name of organization or government: medical university of south carolina. (h) purpose of grant: alzheimer's disease research by takashi sato, phd, entitled: (a2021041s) neural circuit mechanisms underlying sleep disruption in alzheimer's disease model mice. Investigator's summary: sleep disturbance is both an early symptom of alzheimer's disease (ad) in the prodromal phase, and one of the factors that exacerbates ad. This project will study the interaction between sleep and ad progression using advanced microscopy and optical stimulation. Key components of the neural circuts that contribute to sleep will be identified and specific components of the neural circuit will be manipulated during sleep to enhance sleep-related activity in the brain and examine how these manipulations affect ad progression and cognition. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021041s name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by aristeidis sotiras, phd, entitled: (a2021042s) detecting and characterizing preclinical ad using ai and structural mri. Investigator's summary: the proposed project will develop artificial intelligence (ai) tools based on deep learning (dl) that use widely available imaging, cognitive and clinical data to identify individuals that show early signs of alzheimer's pathology and predict their future cognitive performance. Such tools are crucial for improving clinical care by enabling early diagnosis and intervention. Additionally, they can reduce clinical trial costs by enabling targeted recruitment of homogeneous groups of individuals at increased risk of cognitive decline and progression to alzheimer's disease dementia. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021042s name of organization or government: case western reserve university - school of medicine. (h) purpose of grant: alzheimer's disease research by masashi tabuchi, phd, entitled: (a2021043s) clock-driven sleep fragmentations in tauopathy. Investigator's summary: the overall objective of this proposal is to elucidate the role that inactivation states of voltage-gated sodium channels play in the regulation of circadian rhythms and sleep in alzheimer's disease (ad) and related tauopathies. This proposal will test through comparative, both in vivo (drosophila) and in vitro (ips cells), assessments our central hypothesis that manipulations of inactivation states of voltage-gated sodium channels in ad lead to molecular and cellular alterations resulting in dysfunctional circadian rhythms, sleep alterations, and disease progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021043s name of organization or government: mayo clinic jacksonville. (h) purpose of grant: alzheimer's disease research by na zhao, phd, entitled: (a2021046s) apoe genotype-dependent effects of life-style intervention in healthy aging and alzheimer's disease. Investigator's summary: aging and the apolipoprotein e4 (apoe4) gene are the greatest risk factors for late-onset alzheimer's disease (ad). While many therapies have failed in clinical trials, research shows that life-style interventions can delay disease onset. Food restriction has been recognized as one of the most effective ways to extend healthspan, however, it is unclear whether genetically susceptible individuals such as apoe4 carriers can still benefit from preventive life-style interventions. As such, this proposal plans to investigate how diet control or exercise affects brain health using animal models with aging or ad, and with or without the apoe4 gene. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2021046s name of organization or government: mayo clinic, jacksonville. (h) purpose of grant: alzheimer's disease research entitled: (ca2017563) molecular neurodegeneration journal. We partner with biomed central's open acce”

“Name of organization or government: tufts university - boston. (h) purpose of grant: alzheimer's disease research by wonhee kim, phd, entitled: (a2019021f) impact of elevated app on bace1 substrates processing. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2019021f name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by masato maesako, phd, entitled: (a2019056f) visualization of amyloid-beta production. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2019056f name of organization or government: emory university. (h) purpose of grant: alzheimer's disease research by thomas kukar, phd, entitled: (a2019355s) understanding lysosome dysfunction in alzheimer's disease. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2019355s name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by jill goldstein, phd, entitled: (ca2018607) development of clinical algorithm to identify risk for alzheimer's disease in early midlife. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2018607 name of organization or government: johns hopkins university. (h) purpose of grant: alzheimer's disease research by quincy samus, phd, entitled: (ca2021001) dissemination of mind at home dementia care model to drive health care transformation and greater value. Investigator's summary: informed by decades of dementia care clinical expertise, best practice recommendations, and clinical studies, mind at home is an effective, comprehensive, homebased dementia care coordination model that systematically assesses and addresses a broad range of dementiarelated care needs that place elders at risk for health disparities, hospitalizations, unwanted long term care placement, poor quality of life and family caregivers at risk for burnout and health impacts. Yet translation into practice has been slow primarily due lack of data on its potential for return on investment and its value proposition to health systems, health plans, and providers, as well lack of data on how to effectively refine the model to integrate into existing health care delivery environments. This grant supports a partnership with university of maryland baltimore county, jade gong & associates llc, and johns hopkins home care group, with the support of maryland primary care program, maryland medicaid, and johns hopkins alliance for patients to strategically advance the dissemination and translation of john hopkins university's evidencebased mind at home model, in the context of maryland's new primary care program (mdpcp) as a transformative tool to achieve greater care coordination and value for a vulnerable cognitively impaired population. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2021001 name of organization or government: medical technology enterprise consortium. (h) purpose of grant: alzheimer's disease research entitled: (ca2021014) support for proposal mtec-20-16-mtbi-002, advancing the promising cerebroprotectant ast-004 to human traumatic brain injury clinical trials. Investigator's summary: support for proposal mtec-20-16-mtbi-002, advancing the promising cerebroprotectant ast-004 to human traumatic brain injury clinical trials. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2021014 name of organization or government: medical technology enterprise consortium. (h) purpose of grant: alzheimer's disease research entitled: (ca2021015) support for proposal mtec-20-16-mtbi-005, mitochondrial uncoupling prodrug to treat repeated mild traumatic brain injury investigator's summary: support for proposal mte”

“Name of organization or government: foundation for the national institutes of health. (h) purpose of grant: alzheimer's disease research by entitled: (ca2021012) pre-competitive analytical validation of sv2a pet imaging as a biomarker of synaptic density investigator's summary: the sv2a pet project aims to demonstrate the reliability of sv2a pet imaging as a biomarker of synaptic density in alzheimer's disease and accelerate the application of sv2a pet as a treatment response marker in disease-modifying clinical trials. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2021012 name of organization or government: boston university school of medicine. (h) purpose of grant: alzheimer's disease research by benjamin wolozin, md, phd entitled: (ca2020002) development of synthetic gene feedback circuits to prevent tau aggregation. Investigator's summary: this proposal uses a radically novel approach termed "synthetic biology", which uses concepts from electrical engineering to design new types of genetic therapy for alzheimer's disease (ad). We will create new synthetic gene circuits that can detect and then remove harmful tau pathology as it appears in the brains of patients with ad. These new therapies will selectively target only those nerve cells that actually have pathology, increasing the effectiveness while reducing the potential for unwanted side effects. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2020002 name of organization or government: university of denver. (h) purpose of grant: alzheimer's disease research by ann charlotte granholm-bentley, phd, entitled: (ca2018010) international brain bank for down syndrome-related alzheimer's disease investigator's summary: the focus of this special project is to develop a strong collaborate network between six different research groups focused on providing much-needed information about the down syndrome population, of which as many as 80 percent have alzheimer's pathology by the time they are in their 50s and 60s. Although there are many centers and researchers that focus on alzheimer's in the general population, few of them focus on people with down syndrome. The information generated by our project will be of great help to those with down syndrome and those with alzheimer's disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2018010 name of organization or government: the milken institute. (h) purpose of grant: project support for study on neurotechnology that includes identifying areas for future investment in research. Name of organization or government: new york university school of medicine. (h) purpose of grant: national glaucoma research by ji won bang, phd, entitled: (g2021001f) alterations of the sleep-regulating systems in glaucoma. Investigator's summary: this study will use multimodal brain neuroimaging, clinical ophthalmic assessments, and sleep quality assessments in early-stage and advanced-stage glaucoma patients, and healthy subjects. The outcomes should provide a mechanistic account of the high incidence of sleep disorders in glaucoma and could lead to therapeutic advancements benefitting millions of people. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021001f name of organization or government: boston children's hospital. (h) purpose of grant: national glaucoma research by nicholas hanovice, phd, entitled: (g2021002f) augmenting optic nerve regeneration using cell-intrinsic and extrinsic manipulations. Investigator's summary: this proposal will identify the inflammatory cell type that promotes rgc axon regeneration, determining which rgc subtypes extend axons into the injury site, and test whether expanding inflammation further into the optic nerve will enhance long-distance axon regeneration. Results from this proposal will provide mechanistic insight into neuro-immune interactions that stimulate rgc axon regeneration, an”

“Name of organization or government: georgia tech research corporation. (h) purpose of grant: national glaucoma research by babak safa, phd, entitled: (g2021005f) investigating the optic nerve head remodeling in glaucomatous optic neuropathy. Investigator's summary: in this project researcher will: (1) provide the most accurate characterization of the mechanical properties and mechanobiology of the optic nerve head, the primary site of damage in glaucomatous optic neuropathy, and (2) will develop a physiologically-appropriate ex vivo 3d culture model to study the mechanobiologic response of onh cells, thought to drive characteristic changes in glaucoma. This system will eventually form the basis of a high-throughput drug discovery system, accelerating the development of future treatments for glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021005f name of organization or government: boston children's hospital. (h) purpose of grant: national glaucoma research by kimberly wong, phd, entitled: (g2021006f) transcriptional mechanisms that regulate ganglion cell survival and axon regeneration. Investigator's summary: the goal of our research is to investigate how cell death and axon regeneration are regulated by proteins dual leucine zipper kinase (dlk) and leucine zipper kinase (lzk) that are crucial for rgc death. This work can lead to the development of new therapies to halt or even reverse rgc death and vision loss. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021006f name of organization or government: columbia university. (h) purpose of grant: national glaucoma research by revathi balasubramanian, phd, entitled: (g2021007s) mechanisms of angle development and glaucoma. Investigator's summary: in several cases of glaucoma and especially early-onset glaucoma, drainage structures that regulate the eye pressure are affected. To address this, we need to understand the genetics of drainage structure development. We have developed a mouse model of early-onset glaucoma. Using a newly developed mouse model of early-onset and modern imaging methods, researchers will determine how drainage structures develop and the mechanism through which abnormalities in drainage tissue glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021007s name of organization or government: duke university school of medicine. (h) purpose of grant: national glaucoma research by romain cartoni, phd, entitled: (g2021008s) deciphering the local effect of glaucoma risk factors on axonal mitoproteome. Investigator's summary: mitochondria, an intracellular organelle responsible for key cellular processes such as energy production and programmed cell death regulation, have been shown to be impaired in retinal ganglion cells (rgcs) affected by glaucoma. This study will uncover regulators of mitochondrial functions that are affected in glaucomatous conditions which may constitute novel therapeutic targets. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021008s name of organization or government: johns hopkins university. (h) purpose of grant: national glaucoma research by thao nguyen, phd, entitled: (g2021012s) in vivo characterization of the mechanical properties of the human optic nerve head. Investigator's summary: the proposed research aims to measure the deformation of the lamina cribrosa, a connective tissue structure in the optic nerve head that supports the optic nerve axons, in patients caused by a short-term change in the eye pressure by laser suturelysis and wearing tight-fitting swim goggles. The implications of this work can be important to understanding the susceptibility of individuals to glaucoma and to developing new diagnostics techniques and new therapeutic strategies. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021012s name of organization or government: johns hopkins”

“Name of organization or government: university of california, davis. (h) purpose of grant: national glaucoma research by robert zawadzki, phd, entitled: (g2021017s) validation of novel oct based imaging tools for noninvasive longitudinal monitoring of the retinal ganglion cells in animal models of glaucoma. Investigator's summary: novel treatments focused on restoring vision in glaucoma, using gene or stem cell therapies, would benefit from the development of cellular resolution in vivo imaging tools, that could offer sensitivity and specificity beyond current clinical tests. To achieve that we propose to develop and validate novel structural and functional extension of optical coherence tomography (oct), so-called temporal speckle analysis oct (tsa-oct), for basic science research. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2021017s name of organization or government: university of wisconsin-madison. (h) purpose of grant: national glaucoma research by robert w. Nickells, phd, entitled: (g2018166) the pathological contribution of cell adhesion disruption in rgc death. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2018166 name of organization or government: university of illinois at chicago. (h) purpose of grant: national glaucoma research by john hetling, phd, entitled: (g2019356) diagnosing glaucoma in the peripheral retina. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2019356 name of organization or government: georgia institute of technology. (h) purpose of grant: national glaucoma research by c. Ross ethier, phd, entitled: (cg2020001) selective targeting of schlemm's canal inner wall for next-generation glaucoma drugs: subpart a investigator's summary: all treatments for glaucoma seek to lower intraocular pressure (iop), yet existing approaches are insufficient. We now understand that endothelial cell of the inner wall of schlemm's canal (sc) play a key role in homeostatic control mechanisms that maintain iop within a target range. However, tools for directly assessing sc inner wall endothelial function are lacking, as are molecular approaches for directly targeting and interrogating these cells. The long-term goal of this inter-dependent, multiple principal investigator and grantee institution-associated project is to develop novel therapies that directly target sc cells to improve iop control. These targeted therapies will be highly effective due their specificity, and will thus greatly benefit glaucoma patients. To accomplish this goal, we have assembled an outstanding team that brings together all necessary expertise to intervene in this complex system. For more information, visit the brightfocus website: www.brightfocus.org/grant/cg2020001 name of organization or government: duke university. (h) purpose of grant: national glaucoma research by w. Daniel stamer, phd, entitled: (cg2020002) selective targeting of schlemm's canal inner wall for next-generation glaucoma drugs: subpart b investigator's summary: for the project, we will screen candidate adeno associated viruses and engineered promoters cloned into lentiviruses obtained from collaborators in human schlemm's canal cells in vitro and anterior segments ex vivo for selective tropism to/activity in trabecular meshwork versus schlemm's canal. We will utilize recently validated virus technology (enos promoters driving xfp or seap reporter proteins) to transduce schlemm's canal in human anterior segments and monitor shear stress levels and location throughout schlemm's canal. We will provide a steady supply of schlemm's canal cells for development and testing of drug screening platforms. For more information, visit the brightfocus website: www.brightfocus.org/grant/cg2020002 name of organization or government: columbia university. (h) purpose of grant: national glaucoma resea”

“Name of organization or government: university of california, los angeles. (h) purpose of grant: macular degeneration research by antonio escudero paniagua, phd, entitled: (m2021004f) addressing the link about impairment in phagosome degradation and age-related macular degeneration. Investigator's summary: researchers propose to investigate the maturation rate and the accumulation of specific phagosome (a vesicle formed around a particle engulfed by a phagocyte cell) stages in rpe cells from macular dystrophy patients in comparison to cells from healthy patients and mice models. . These studies will provide a paradigm shift in our identification and understanding of the etiology of macular dystrophys and could be key for the development of new strategies to stop or prevent them. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021004f name of organization or government: university of pittsburgh. (h) purpose of grant: macular degeneration research by sayan ghosh, phd, entitled: (m2021005f) understanding the role of akt2 signaling in inflammatory processes in age-related macular degeneration. Investigator's summary: in this proposal, using their genetically engineered mouse models, researchers aim to understand if their gene of interest regulates retinal inflammation and degeneration as seen in age-related macular degeneration (amd), through the interaction between infiltrating inflammatory cells (neutrophils) and the immune cells (retinal microglia). Understanding these molecular changes may provide novel background for future drug discoveries for atrophic amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021005f name of organization or government: university of pennsylvania. (h) purpose of grant: macular degeneration research by rohini m nair, phd, entitled: (m2021007f) exploring the role of hepatic lipase and lipid metabolism in age-related macular degeneration pathogenesis. Investigator's summary: this study aims to unravel the role of hepatic lipase (hl) that breaks down high-density lipoproteins (hdl) to smaller denser particles to be cleared away by systemic circulation. Understanding its role in regulating cholesterol efflux using cellular (ipsc derived rpe cultures) and animal models would help design targeted therapies for slowing down the disease progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021007f name of organization or government: stanford university. (h) purpose of grant: macular degeneration research by ke ning, md, entitled: (m2021008f) ciliary lipids in rpe repair: a novel target for age-related macular degeneration (amd). Investigator's summary: researchers in this study have discovered a novel role of rpe cilia (that looks like an antenna) that is related to the control of rpe repair in mice; loss of these organelles promotes cell proliferation and wound healing. They propose to study how this organelle mediates cell proliferation and wound healing. The result of this study will help us understand how antenna works in rpe proliferation and targeting this mechanism for drug development in amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021008f name of organization or government: national eye institute, nih. (h) purpose of grant: macular degeneration research by davide ortolan, phd, entitled: (m2021009f) macular and mid-peripheral specific ipsc-rpe models to discover regional rpe susceptibility in age-related macular degeneration (amd). Investigator's summary: this study will identify molecular and physiological differences between the two populations of rpe cells (derived from the central and the peripheral retina) in a dish and will find which properties make the central rpe more vulnerable than peripheral rpe. With this new knowledge, plus having an easily reproducible model in a dish, will eventually translate in the development of drugs to prevent vision”

“Name of organization or government: university of california, irvine. (h) purpose of grant: macular degeneration research by andrew browne, md, phd, entitled: (m2021013n) functional imaging of the human retina using two-photon ophthalmoscopy. Investigator's summary: this proposal seeks to develop a camera for use in humans and directly examine the causes of age-related macular degeneration in human subjects. Researchers will translate the 2-photon (2p) microscopy technology already established to study models to a device that can non-invasively acquire images at such high resolution that they can reveal what is happening inside cells. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021013n name of organization or government: massachusetts eye and ear infirmary. (h) purpose of grant: macular degeneration research by rosario fernandez godino, phd, entitled: (m2021014n) biomechanical properties of the bruch's membrane and their relevance to the rpe pathology in age-related macular degeneration. Investigator's summary: in this proposal, researchers will evaluate the rigidity of eyes with and without age-related macular degeneration (amd) and how the elasticity of the retina impacts the function of the retinal cells. The results will contribute to bridge the gaps between aging and amd as well as to improve existing therapeutic approaches for amd patients, such as the rpe transplantation. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021014n name of organization or government: university of california, san francisco. (h) purpose of grant: macular degeneration research by tyson kim, phd, entitled: (m2021015n) elucidating the origin and arteriovenous identity of chorioretinal anastomoses in a model of type 3 neovascular age-related macular degeneration. Investigator's summary: in order to study the formation of chorioretinal anastomoses (cra), which is a lesion formed by the vascular fusions between the retinal and choroidal vascular networks, researchers in this study will develop an advanced imaging method to look deeper into the living eye with cellular resolution, molecular information, and the ability to measure blood flow down to individual microvessel in neovascular age-related macular degeneratio (amd) models. This will provide insights to help develop more effective treatments for neovascular amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021015n name of organization or government: northwestern university, feinberg school of medicine. (h) purpose of grant: macular degeneration research by jeremy lavine, md, phd, entitled: (m2021016n) macrophage origin, heterogeneity, and function during experimental choroidal neovascularization in mice. Investigator's summary: the premise of this study is that there are macrophage (immune cell) subtypes, and classically-derived macrophages promote wet age related macular degeneration (amd), while non-classical macrophages block wet amd. This group has identified a macrophage subset that expresses blood vessel growth factors derived from classical macrophages and is present in patients with wet amd. They further aim to identify non-classical-derived macrophage subsets and demonstrate that they inhibit experimental wet amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2021016n name of organization or government: baylor college of medicine. (h) purpose of grant: macular degeneration research by rinki ratnapriya, phd, entitled: (m2021017n) functional characterization of genetic regulatory effects of age-related macular degeneration (amd) risk variants. Investigator's summary: in this proposal, researchers will integrate the genome-wide associated studies (gwas) findings with transcriptome (protein coding region) and epigenome (dna modification markers) data to identify underlying causal variants, regulatory elements and target genes to address major gaps in”