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, 300 million people worldwide suffer from these diseases. Brightfocus has a proven track record of supporting the most innovative, early-stage research seeking to foster a better understanding of, treatments for, and ultimately, a cure for, these age-related diseases with no cure. Since 1973, brightfocus has awarded more than $287 million in research grants to thousands of scientists around the world. Our research funding has led to major contributions to understanding 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 10 times 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, and 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 for 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 (view our research milestones on brightfocusbold.org.) brightfocus also 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 (psas) 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 seeks 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 2023, these psa messages generated $25,308,680 in donated media services and garnered over 532 million impressions. 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 to better educate the public on the latest research developments pertaining to alzheimer's, macular degeneration, and glaucoma, as well as the importance of equitable participation in clinical research to accelerate the path to cures for neurodegenerative diseases. Specifically, brightfocus is producing and disseminating free programs including: - brightfocus chats, since 2014, these audio discussions have brought together patients and caregivers for interactive monthly telephone forums to learn from and ask questions of leading vision”

“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 55 million people worldwide have alzheimer's disease or other dementias, with women and other minority groups most at-risk. Brightfocus' alzheimer's disease research (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 its inception, brightfocus has contributed more than $175 million to the conquering of alzheimer's disease. During the fiscal year that ended march 31, 2023, adr awarded $6,394,521 in peer-reviewed grant awards to 26 new research projects and 8 other awards to make a total of 34 grants at $7,755,537 total in funding. Notable projects include: hypertension and lifestyle effects on risk of alzheimer's (including lipids); drug discovery and biomarkers; the role of inflammation, microglia, and vascular health in disease risk; looking at the mitochondria and cell energy deficiencies; the role of sleep disturbances causing an increased risk of cognitive issues; differences in genetics and disease risk for underrepresented populations; and better use of modern technologies, including big data/ai 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," the official journal of brightfocus foundation and the number one open-access journal in neuroscience. 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 available free of charge. This open access ensures maximum reach of journal content to scientists and health care providers worldwide. In addition to supporting cutting-edge research, adr 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. At least 20 million americans have some type of macular degeneration, including both the early and later stages of the wet and dry types. Macular degeneration research (mdr ), a program of brightfocus, has awarded nearly $50 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 imaging, machine learning and 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, 2023, mdr awarded $3,839,035 in peer-reviewed grant awards to 13 new research projects, with 5 additional projects that take the total funding to 18 grants at $4,039,275. Details about specific projects are included in schedules f & i. In addition to supporting cutting-edge research, mdr 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. According to a recent report from the world health organization, approximately 80 million people around the world have glaucoma. More than three million americans over the age of 40 are living with glaucoma, with an estimated 2.7 million have open-angle glaucoma, the most common type. 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. It is estimated that only half of the people living with glaucoma are aware that they have the disease. Brightfocus' ngr program has awarded more than $49 million worldwide for the study of glaucoma. Ngr-supported research has been focused on the eye-brain connection, how pressure buildup in the eye can affect synaptic nerve communications, neuroprotection, and optic nerve regeneration, discovering glaucoma risk genes, ai/deep learning and adaptive optics, sleep disturbance and risk of developing glaucoma, developing early glaucoma screening, and pursuing novel genetic counseling and communication strategies, amongst other innovative pursuits. Brightfocus' national glaucoma research (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, 2023, ngr awarded $2,034,241 in peer-reviewed grant awards for 11 new projects and 2 other awards to make a total of 13 grants at $2,526,791 in funding. Details about specific projects are included in schedules f & i. In addition to supporting cutting-edge research, brightfocus' ngr program 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 1,028,552. Change in present value of grants 267,164.”

“Region: europe (d) purpose of grant: alzheimer's disease research by lucia chavez-gutierrez, phd, entitled: (a2023005s) elucidating the mechanisms of action of gamma-secretase modulators (gsms) to facilitate structure-based design of next-generation therapeutics. Investigator's summary: alzheimer's disease (ad) is linked to the build-up of longer, aggregation-prone amyloid-beta (a-beta) peptides in the brain. Gamma-secretase dysregulation leading to enhanced production of longer a-betas causes ad. Gamma-secretase modulators promote the production of shorter a-betas, while sparing critical (gamma-secretase) biological roles. These molecules are promising agents in the fight against ad; however, a lack of understanding of their modes of action have limited their development. Here, we will define the mode(s) of action of gamma-secretase modulators and foster therapeutic development. Grant awarded: $300,000, flanders institute for biotechnology, (vib), gent, belgium. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023005s region: europe (d) purpose of grant: alzheimer's disease research by marta casquero-veiga, phd, entitled: (a2023012f) development of multimodal neuroimaging biomarkers of the pro-coagulant state in alzheimer's disease (nipad). Investigator's summary: alzheimer's disease (ad) pathophysiology includes an early hemostatic dysregulation, inducing a pro-thrombotic milieu. Consequently, ad-patients' brains show increased fibrin levels and degradation-resistant clots, which contributes to neuronal death. These processes appear early in ad's course, but not in all patients. This study aims to develop new generation probes to visualize the pro-coagulant components accumulated in the ad brain, by in vivo non-invasive multimodal imaging. Ultimately, outcomes will enable clinicians to prescribe a suitable treatment to ameliorate ad's progression. Grant awarded: $200,000, instituto de investigacion sanitaria - fundacion jimenez diaz, madrid, spain. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023012f region: europe (d) purpose of grant: alzheimer's disease research by qi wang, phd, entitled: (a2023018f) restoring mitochondrial homeostasis as a therapy of alzheimer's disease. Investigator's summary: defects in mitochondria precede the onset of dementia by decades and are involved in multiple aspects of alzheimer's disease (ad) pathogenesis. I aim to test whether activating the beneficial mitochondrial stress responses with a compound named 9-tb could improve ad pathologies. I will investigate 9-tb's effects on mitochondrial function, main cognitive and biomedical manifestations of ad in a mouse model. I will use advanced multi-omics approach to fully reveal 9-tb's mechanisms of action and validate its mechanism using in vitro, ex vivo and in silico systems, fulfilling the requirements for clinical trials. Grant awarded: $200,000, swiss federal institute of technology lausanne, switzerland. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023018f region: middle east (d) purpose of grant: alzheimer's disease research by ariel gilad, phd, entitled: (a2023024s) brain-wide network dysfunctions in alzheimer's disease of individual mice. Investigator's summary: a hallmark of alzheimer's disease (ad) is abnormal brain-wide networks that differ across and within patients. Here, we aim to use an ad mouse model to record brain-wide networks in mice during ad-related cognitive tasks. By using an individual approach and track each mouse throughout its lifespan, we believe that each mouse will display brain-wide dysfunction that is modulated based on ad progression and individual traits. We aim to outline key brain areas that may be targeted in individual human patients using deep-brain stimulation, thus increasing the quality of life for millions of people grant awarded: $300,000, hebrew university of jerusalem, israel. For more information”

“Region: europe (d) purpose of grant: national glaucoma research by karen peynshaert, phd, entitled: (g2023002f) exploring icg-mediated ilm photodisruption as a tool to boost retinal ganglion cell engraftment. Investigator's summary: this project explores an innovative biophotonic approach to manipulate the inner limiting membrane (ilm), a barrier which greatly hinders the retinal entry of donor rgcs following intravitreal injection. By controlled perforation of the ilm, we aim to enhance the migration of rgcs into the retina while maintaining ilm's cues necessary for their subsequent development. Grant awarded: $150,000, ghent university, gent, belgium. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2023002f region: north america (d) purpose of grant: national glaucoma research by adriana di polo, phd, entitled: (g2023005s) disease-modifying mitochondrial uncouplers: a new therapeutic strategy for glaucoma. Investigator's summary: mitochondrial dysfunction is a key feature of neuronal damage in glaucoma. This proposal will test the potential of mild mitochondria uncouplers as disease-modifying agents to reduce oxidative stress, improve calcium homeostasis, and promote repair pathways. The outcome of this study will provide robust proof-of-principle data and open new opportunities for clinical testing in glaucoma patients. Grant awarded: $200,000, university of montreal, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2023005s region: europe (d) purpose of grant: national glaucoma research by silvia marinelli, phd, entitled: (g2023006s) a new optimized form of nerve growth factor: an anti-inflammatory and neuroprotective drug candidate for glaucoma. Investigator's summary: we developed an optimized nerve growth factor, painless ngf (ngfp), that has the same neuroprotective properties as natural ngf but lacks adverse effects, such as pain and cell death signalling. Ngfp, without the pitfalls of natural ngf, is a promising therapeutic candidate for glaucoma, able to rescue rgc degeneration through a synergistic action of neuroprotection and inflammatory modulation grant awarded: $200,000, fondazione ebri "rita levi-montalcini", rome, italy. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2023006s region: europe (d) purpose of grant: national glaucoma research by darryl overby, phd, entitled: (g2023011s) microenvironmental regulation of barrier function in schlemm's canal endothelial cells. Investigator's summary: the only way to treat glaucoma is to reduce eye pressure, but the factors controlling eye pressure are not understood. Our lab has shown that eye pressure is partly regulated by a layer of specialised cells that create a barrier against fluid drainage from the eye. We aim to recreate this cellular barrier in the lab, which will open new avenues for research and development targeting this barrier. Grant awarded: $184,242, imperial college of science, technology and medicine, london, united kingdom. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2023011s region: europe (d) purpose of grant: national glaucoma research by darryl overby, phd, entitled: (cg2020003) developing new drugs to lower eye pressure in glaucoma. Investigator's summary: 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 will develop and apply novel screening technologies to identify new drugs to lower eye pressure by improving aqueous humor drainage across schlemm's canal cells. Grant awarded: $97,975, imperial college of science, technology and medicine, london, united kingdom. For more information, visit the brightfocus website: www.brightfocus.org/grant/cg2020003 region: east asia & pacific (d) purpose of grant: macular degeneration research by matthew rutar, phd, entitled: (m2023009n) i”

“Name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by zahra shirzadi, phd, entitled: (a2023001f) novel tools to dissect the multi-factorial etiologies of white matter injury in aging and alzheimer's disease. Investigator's summary: the brain's white matter is composed of millions of bundles of nerve fibers that connect neurons in different brain regions into functional circuits. Therefore, any damage to these fibers can affect normal brain function. It is very common to observe signs of white matter injury in brain images of preclinical and symptomatic alzheimer's disease (ad) patients, yet it is unclear why this injury occurs. Following up on our recent studies in familial ad, we will investigate whether ad markers including amyloid accumulation and brain tissue loss can describe white matter injury in ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023001f name of organization or government: baylor college of medicine. (h) purpose of grant: alzheimer's disease research by daheun chung, phd, entitled: (a2023002f) exploring the protective role of the big tau isoform in alzheimer's disease. Investigator's summary: as cognitive decline is highly correlated with the severity of tau pathology in alzheimer's disease, protecting tau from abnormal changes may bring therapeutic benefits. While there is no effective tau-targeting treatment, i recently discovered that an understudied tau isoform, abundant in the brain region spared from tau pathology, is less likely to become pathologically altered. As such, i propose to examine if this tau isoform is crucial in preventing the development of tau pathology in the brain, and if it has any unique interacting protein partners that facilitate such a phenomenon. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023002f name of organization or government: northwestern university feinberg school of medicine. (h) purpose of grant: alzheimer's disease research by david gate, phd, entitled: (a2023003s) proteogenomics to study adaptive immunity in neurodegenerative disease. Investigator's summary: this proposal will utilize a novel proteogenomics approach to explore the role of adaptive immune t cells in the pathophysiology of age-related neurodegeneration. This approach aims to identify neuroimmunologic disease mechanisms and therapeutic targets for these devastating diseases. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023003s name of organization or government: johns hopkins university school of medicine. (h) purpose of grant: alzheimer's disease research by meaghan morris, md, phd, entitled: (a2023004s) exploring the origins of tau pathology in human brain: molecular signatures of aging and neurodegeneration in the locus ceruleus. Investigator's summary: the spread of tau pathology in alzheimer's disease is associated with progressive cognitive decline. However, the molecular events surrounding the earliest formation and spread of tau pathology in the human brain are largely unexplored. This study will examine the molecular environment associated with aging and early accumulation of tau pathology in human brain, as well as the earliest spread of tau pathology in aging and alzheimer's disease. Insight into this early tau formation could provide targetable pathways to prevent the formation or spread of tau pathology in the brain. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023004s name of organization or government: cornell university. (h) purpose of grant: alzheimer's disease research by matthew isaacson, phd, entitled: (a2023006f) imaging neural activity changes underlying the acute rescue of memory function after improving cerebral blood flow in alzheimer's disease mouse models. Investigator's summary: using visual and spatial behavioral tasks during functional brain imaging, we will cha”

“Name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by jingyuan chen, phd, entitled: (a2023011s) whole-brain sleep-wake energetics in subjects at genetic risk for alzheimer's disease. Investigator's summary: recent rodent studies have suggested that disrupted synaptic activity across sleep-wake cycles plays an important role in causing alzheimer's disease (ad). In this proposal, we will leverage cutting-edge human imaging techniques to test whether such abnormalities of cyclic neuronal activity across sleep-wake cycles can be identified in subjects at genetic risk for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023011s name of organization or government: northwestern university feinberg school of medicine. (h) purpose of grant: alzheimer's disease research by arun upadhyay, phd, entitled: (a2023013f) stable isotope-based dating of the amyloid fibril proteome. Investigator's summary: the recent success of antibody-based therapeutics targeting various forms of a-beta peptides highlights the importance of amyloid fibrils in ad pathology. Notably, fibril dynamics is one of the most crucial factors affecting amyloid deposition during ad progression. In this application, i propose to (1) identify proteins associated with newly formed amyloid fibrils in the brain; (2) investigate if manipulating these proteins influences the onset of amyloid pathology. Ultimately, this project will uncover new aspects of amyloid kinetics and may provide new targets for reducing amyloid pathology. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023013f name of organization or government: weill medical college of cornell university. (h) purpose of grant: alzheimer's disease research by sung ji ahn, phd, entitled: (a2023014f) neurovascular and neuronal network dysfunction in tauopathy mouse models. Investigator's summary: alzheimer's disease (ad) is the leading causes of dementia, currently untreatable. A major culprit that damages the brain in ad is the protein "tau." tau molecules are normal constituents of brain cells but when chemically altered form clumps that clog up in the cells. We seek to find out if tau clumps are damaging by starving the brain of its blood supply, which carries vital oxygen and nutrients necessary for normal brain function and survival. We will also test if providing extra oxygen to the brain can overcome the brain dysfunction caused by tau, which could have therapeutic implications. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023014f name of organization or government: johns hopkins university school of medicine. (h) purpose of grant: alzheimer's disease research by alyssa coyne, phd, entitled: (a2023015s) escrt-iii nuclear surveillance in chmp2b ftd. Investigator's summary: maintenance of the protein complexes that control communication between the nuclear and cytoplasmic compartments of cells is essential for proper neuronal function and survival. Recent work has demonstrated that defects in a nuclear surveillance pathway initiate damage to these cellular communication channels as an early and significant event in lou gehrig's disease. This proposal will examine the contribution of impaired nuclear surveillance and nuclear-cytoplasmic compartmentalization to a genetically linked form of dementia. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023015s name of organization or government: university of southern california. (h) purpose of grant: alzheimer's disease research by paul seidler, phd, entitled: (a2023016s) unfolding alzheimer's tau therapies: approaches for the near- and long-term. Investigator's summary: by no mistake, natural product chemicals in the forms of vitamins and dietary supplements have long played a role in supporting human health. In the context of aging, plant natural products evolved alongsid”

“Name of organization or government: yale university. (h) purpose of grant: alzheimer's disease research by carla rothlin, phd, entitled: (a2023022s) functional understanding of axl effector role(s) in microglia towards developing disease modifying therapies in alzheimer's disease. Investigator's summary: we have identified a protein expressed in brain immune cells that makes these cells better at protecting against alzheimer's disease (ad). Here we envision to understand exactly how this protein functions by engulfing and removing a-beta plaques or by dampening inflammation to prevent ad-associated neuroinflammation. We will also better understand the sequence of events leading to the improved activity of this protein that protects against cognitive decline. This knowledge will enable us to develop therapeutics to improve disease outcome in ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023022s name of organization or government: university of california, san diego. (h) purpose of grant: alzheimer's disease research by subhojit roy, md, phd, entitled: (a2023023s) therapeutic gene-editing in alzheimer's disease. Investigator's summary: our overall goal is to take a crispr based gene therapy for alzheimer's disease (ad) to the clinic. Broadly speaking, our approach restores the physiologic balance of the amyloid pathway decreasing neurotoxic protein fragments, while promoting neuroprotective protein fragments. There are over 100 ongoing clinical trials worldwide using crisprs, and the results so far with non-neurologic disorders have shown unprecedented (almost 100%) efficacy. Our broad vision is to apply crisprs for devastating neurologic illnesses like ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023023s name of organization or government: university of kentucky. (h) purpose of grant: alzheimer's disease research by daniel c. Lee, phd, entitled: (a2023025s) citrullinated tau as a therapeutic target in tauopathies. Investigator's summary: alzheimer's disease (ad) continues to impact neuronal health. Tau pathology is diverse despite being a single protein and also remains the closet corollary to memory loss and neurodegeneration. Tau diversity likely comes from different cellular modifications on the tau protein. We discovered a new modification on tau called citrullination which changes the amino acid arginine to a citrulline. We hypothesize that citrullination to tau causes more toxicity in the brain. We will test citrullination inhibitors and vaccines against citrullinated tau in mice that develop hallmarks of ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2023025s name of organization or government: mayo clinic, jacksonville. (h) purpose of grant: alzheimer's disease research by entitled: (ca2021010) molecular neurodegeneration journal. Investigator's summary: the aim of molecular neurodegeneration (mn) journal (https://molecularneurodegeneration.biomedcentral.com/) is to serve the scientific community by publishing high-impact, high-quality, and front-line research discoveries in diverse areas of neurodegenerative diseases including alzheimer's disease and eye-related degenerative conditions. Mn is the official journal of the brightfocus foundation. All articles are free and permanently accessible online, without subscription charges or registration barriers. The journal has seen further growth in recent years in particular in the area of scientific impact and reputation. Some of these are reflected in the following metrics: 1) the impact factor of molecular neurodegeneration, the official scientific journal of brightfocus foundation, has risen to 18.879, according to its publisher, up from 14.195 a year ago (33% increase).; 2) it is now the top-ranked open-access publication in its field, on par with other high-impact journals including neuron, journal of experimental medicine and nature communications. A scie”

“Name of organization or government: university of colorado. (h) purpose of grant: alzheimer's disease research by lotta granholm, phd, entitled: (ca2018010) international brain bank for down syndrome-related alzheimer's disease. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2018010 name of organization or government: university of southern california. (h) purpose of grant: alzheimer's disease research by jinkook lee, phd, entitled: (ca2023001) expanding and enhancing lasi-dad for better understanding of alzheimer's disease and dementia. Investigator's summary: this project will expand and enhance the ongoing longitudinal aging study in india diagnostic assessment of dementia (lasi-dad) by exploring how dna methylation of alzheimer's associated genes is associated with cognition and dementia. It will further validate previous findings from the lasi-dad to compare the accuracy of findings with gold standard measures of cognition and blood biomarkers. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2023001 name of organization or government: university of california, berkeley. (h) purpose of grant: national glaucoma research by shubham maurya, phd, entitled: (g2023001f) regulation of microglial phenotype by neuroprotective lxb4 in ocular hypertension-induced neuropathy. Investigator's summary: we had identified a novel way to stop the death of retinal cells in mice glaucomatous eyes using small molecule lipid mediators. These lipid mediators have bioactions in modulating the functions of a resident immune cell type in the retina, i.e., microglia. This project intends to study the regulation of microglia by lipids mediators during glaucoma progression to stop or prevent the disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2023001f name of organization or government: university of wisconsin-madison. (h) purpose of grant: national glaucoma research by kazuya oikawa, phd, bvsc, entitled: (g2023003f) modulation of neuroinflammation in glaucoma by glp-1r agonist. Investigator's summary: inflammation of the nervous system tissue contributes to blinding loss of nerve cells in the eye and brain in glaucoma. In this project, we aim to repurpose an existing fda-approved drug to modify this inflammatory response with the goal of identifying a potential new therapy to help preserve vision in patients with glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2023003f name of organization or government: university of california, berkeley. (h) purpose of grant: national glaucoma research by karthik shekhar, phd, entitled: (g2023004s) a spatial transcriptomics approach to identify molecular changes and multicellular interactions underlying retinal neurodegeneration in glaucoma. Investigator's summary: to identify novel molecular targets that can slow down relentless retinal ganglion cell (rgc) death in glaucoma, we need to understand molecular pathways and multi-cellular interactions that underlie rgc susceptibility. We will combine innovative spatial profiling technologies, mouse models, and machine learning to understand rgc degeneration and the role of the microenvironment in glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2023004s name of organization or government: georgia tech research corporation. (h) purpose of grant: national glaucoma research by mark prausnitz, phd, entitled: (g2023007s) non-drug, non-surgical hydrogel-based treatment of glaucoma. Investigator's summary: reducing intraocular pressure (iop) is the only glaucoma treatment, but is often ineffective due to poor patient compliance and surgical complications. We developed a non-drug, non-surgical method to lower iop by injecting a hydrogel to expand the suprachoroidal space of the eye. Here we optimize the hydrogel to prolong iop lowering, evaluate”

“Name of organization or government: international society for eye research. (h) purpose of grant: national glaucoma research travel grants for conference attendance. 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 research by simon john, phd, entitled: (cg2020004) selective targeting of schlemm's canal inner wall for next-generation glaucoma drugs: subpart d. Investigator's summary: the project aims to develop and test resources for schlemm's canal specific targeting and expression of genes for gene therapy. Successful development of this targeted therapy will help control eye pressure more effectively and provide better treatment options for glaucoma patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/cg2020004 name of organization or government: stanford university. (h) purpose of grant: national glaucoma research by jeffrey goldberg, phd, entitled: (cg2022001) a randomized, sham controlled, masked phase ii study to evaluate the safety and efficacy of dual intravitreal implantation of neuroprotective cell therapy for the treatment of glaucoma. Investigator's summary: the proposed project is an extension of the current phase 2 clinical trial, to assess and validate the use of dual nt-501 cntf encapsulated cell therapy (ect) on visual impairment related to glaucoma, in human subjects. The proposed study is designed to expand our knowledge of the dose-dependent effect of cntf in glaucoma through dual implantation of nt-501 ect. For more information, visit the brightfocus website: www.brightfocus.org/grant/cg2022001 name of organization or government: the jackson laboratory. (h) purpose”

“Name of organization or government: university of washington. (h) purpose of grant: macular degeneration research by rayne lim, phd, entitled: (m2023004f) factor h-like protein 1 insufficiency in retinal pigment epithelium. Investigator's summary: early onset macular drusen (eomd) is an inherited, severe form of age-related macular degeneration (amd). We found that retinal pigmented epithelium (rpe) cells made from eomd patients have decreased (about 50%) expression of two important complement proteins, cfh and fhl-1. This significant decrease may alter local complement activity and rpe metabolism. We will study eomd patient rpe, their gene-edited controls, and determine whether adding the fhl-1 gene back to the eomd cells will help attenuate these pathogenic changes. This project will help our understanding of amd disease pathogenesis and treatment. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2023004f name of organization or government: university of california, san francisco. (h) purpose of grant: macular degeneration research by sangeetha kandoi, phd, entitled: (m2023005f) photoreceptor remodeling in the hibernating cone-dominant 13-lined ground squirrel as a model for macular degeneration in humans. Investigator's summary: the cone photoreceptors exclusively populate the small central region within the human retina and provide high acuity, and color vision. The loss of cones is an endpoint of age-related macular degeneration (amd), the leading cause of blindness in individuals >50 years old. Our study utilizes 13-lined ground squirrel (13-lgs), which has 85% cones overall and hibernates in winter. The abundance of cones, and evolved protection against hibernation stress on cones suggest that the 13-lgs could be a clinically relevant model for exploring innovative therapies for catastrophic vision loss in amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2023005f name of organization or government: washington university in st. Louis. (h) purpose of grant: macular degeneration research by james walsh, md, phd, entitled: (m2023006f) dysregulated choroidal adaptive immunity exacerbates macular degeneration pathology. Investigator's summary: macular degeneration is one of the leading causes of blindness in the us, yet the exact disease process that leads to the findings of this disease are not known. There have been consistent studies that show that the adaptive immune system is altered systemically, but because the eye has a reputation for being immune privileged, the role of the local adaptive immune system in this process has not been explored. We recently discovered that there is a rich adaptive lymphoid environment in the choroid that could contribute to the disease process, and will explore this further in this proposal. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2023006f name of organization or government: the university of iowa. (h) purpose of grant: macular degeneration research by narendra pandala, phd, entitled: (m2023007f) autologous choroidal endothelial cell replacement for the treatment of amd. Investigator's summary: age related macular degeneration is a leading cause of blindness in the u.s. In the dry form of the disease, the macula, which is the central most part of the retina that is responsible for high acuity vision, deteriorates. Recent studies have shown that the capillaries present underneath the retina in the choroid are lost before retinal degeneration. In this project, we propose to develop an early intervention strategy to transplant patient-derived choroidal stem cells using a biomaterial to repopulate the lost capillaries in the choroid and thus prevent further damage to the retina. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2023007f name of organization or government: oregon health & science university. (h) purpose of grant: macular degeneration research”

“Name of organization or government: university of california, irvine. (h) purpose of grant: macular degeneration research by dorota skowronska-krawczyk, phd, entitled: (m2020271) role of elovl2 in age related changes in the eye. Emergency relief supplement due to covid-19. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020271 name of organization or government: helen keller foundation for research & education. (h) purpose of grant: 2022 helen keller prize for vision research partnership. The helen keller prize for vision research recognizes significant accomplishments in vision research, and provides funds for continuance of those studies. Name of organization or government: helen keller foundation for research & education. (h) purpose of grant: 2022 conference support. Name of organization or government: arvo foundation for eye research. (h) purpose of grant: 2022 eyefind research grant sponsorship name of organization or government: arvo foundation for eye research. (h) purpose of grant: 2022 travel grants for conference attendees”