Brightfocus Foundation

“A draft of the federal form 990 shall be distributed to the audit committee for review prior to being submitted to the internal revenue service. The draft federal form 990 shall be 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 shall be 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 annaually. 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 the budget approved by the board of directors. The president/ceo and human resources review employee compensation and benefits that includes 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 foundation drives innovative research worldwide and promotes awareness of alzheimer's macular degeneration, and glaucoma. Our vision is living 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 more than $176 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 to the awarding of two nobel prizes. Brightfocus-supported findings are consistently cited by other scientists at twice the frequency as other research findings. 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 10 times larger than the original brightfocus award. This one thousand percent 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. Indisputably, the world-class research identified and supported by brightfocus is more than promising: it is making a real contribution to revolutionary science in the fight to save mind and sight. Along with funding cutting-edge research to find cures to some of society's costliest diseases, brightfocus also provides free educational materials and support to hundreds of thousands of patients and families affected by these diseases nationwide. We base these educational materials off of 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. Both 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 and supermarkets. In fiscal year 2017, these psa messages generated $15,795,314 in donated media services and garnered 1.6 billion impressions. Starting in february 2014, we launched brightfocus chats, a free, interactive monthly telephone forum that brings together patients and caregivers 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. We have expanded our written content of key research findings, promoting and sharing this information through our web site and social media platforms. Capitalizing on emerging use of data visualization, our brightfocus infographics easily and visually communicate information on alzheimer's, macular degeneration, and glaucoma. More specifically, each of these program areas mail awareness-raising materials to hundreds of thousands of households, with messages focusing on: - risk factors and symptom recognition”

“Recoveries of prior year grants 37,128. Change in present value of grants 60,260.”

“Region: europe (d) purpose of grant: alzheimer's disease research by mar hernandez guillamon, phd entitled: (a2017243s) therapeutic effect of rapoa-i-milano in an alzheimer's disease model. Investigators summary: beta-amyloid (a-beta) protein is abnormally accumulated in brains of patients with alzheimer's disease (ad), which is believed to be a sufficient cause to induce cell death of neurons. Different evidences suggest that the levels and distribution of lipids in the brain influence the transport and the deposition of a-beta protein. The aim of this proposal is to determine the effect of a new treatment based on the administration of a natural modified protein able to mobilize lipids in a transgenic mice model of ad. This protein, the apoa-i-milano variant, has been shown to be protective in cardiovascular diseases; however its properties have never been tested in brain diseases before. Grant awarded: $300,000, vall de hebron research institute, barcelona, spain. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017243s region: north america (d) purpose of grant: alzheimer's disease research by randy mcintosh, phd entitled: (a2017286s) building a personalized virtual brain with alzheimer's disease to guide clinical decisions. Investigators summary: the brain is a complicated system where different parts interact to support a variety of cognitive functions. This complexity makes it difficult to treat diseases such as alzheimer's and parkinson's where many different brain areas can be affected, but lead to very similar deficits such as memory dysfunction. Our research provides a framework with tools to "reconstruct" the brain, building models of different dementias to characterize the unique features of each disease and the final common paths to cognitive impairment. As our work progresses, it will be used to evaluate the potential of therapeutic interventions to help identify targets that are most likely to have the best outcome for the individual. Grant awarded: $299,565, baycrest centre for geriatric care, toronto, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017286s region: europe (d) purpose of grant: alzheimer's disease research by daniel bos, md, phd entitled: (a2017424f) progression of atherosclerosis: the influence on brain structure, cognitive function and dementia. Investigators summary: atherosclerosis - or hardening of the arteries - is increasingly being recognized as an important risk factor for dementia. Yet, it remains unclear whether the progression of atherosclerosis at different locations in the arterial system also contributes to changes in the structure or function of the brain and ultimately dementia. However, the knowledge on the dynamics of atherosclerosis and its role in these brain changes and dementia will greatly improve our insight into the development of the disease. Subsequently, this may even offer therapeutic or preventive opportunities to reduce the number of persons suffering from dementia by targeting atherosclerosis. Grant awarded: $98,823, erasmus medical center, rotterdam, netherlands. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017424f region: europe (d) purpose of grant: alzheimer's disease research conference support. Grant awarded: $96,265, the 13th international conference on alzheimer's & parkinson's diseases, vienna, austria.”

“Region: north america (d) purpose of grant: national glaucoma research by martin steinbach, phd entitled: (g2017093) disruption of inter-hemispheric transfer in early glaucoma. Investigators summary: glaucoma is known as the "silent killer of vision" because a large proportion of people are not aware they have it until the late stages of disease, and therefore it is very important to detect the disease early so these patients get help. It is also important to understand the disease in order to develop new lines of treatments. There is new indication that changes occur not only in the eyes, but also in the brain of these patients, particularly in a structure that connects the two brain hemispheres. We plan to test the function of this brain structure using a series of non-invasive tests. Grant awarded: $150,000, vision science research program, krembil institute, toronto, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017093 region: north america (d) purpose of grant: macular degeneration disease research by sarah mcfarlane, phd entitled: (m2017002) molecular regulation of choroid neovascularization. Investigators summary: in neovascular age-related macular degeneration (amd) sprouting of new blood vessels (angiogenesis/neovascularization) leads to death of the nerve cells of the retina. Neovascular amd places a substantial burden on patients and the health care system. Current approaches to block new blood vessels from forming are not effective in many patients and they have serious side-effects. To address an urgent need effective ways to prevent these faulty new blood vessels from forming, but not affect the health of retinal nerve cells or the normal blood vessels, we are developing a genetic animal model where we can rapidly identify novel, safe and effective drugs for the treatment of neovascular amd. Grant awarded: $158,521, university of calgary, calgary, canada. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017002”

“Name of organization or government: northwestern university. (h) purpose of grant: alzheimer's disease research by shahrnaz kemal, phd entitled: (a2017033f) tau-independent microtubule defects in alzheimer's disease: the potential for new drug targets. Investigator's summary: alzheimer's disease (ad) is the most common cause of dementia and the sixth leading cause of death in the us. Finding new therapies to prevent and treat ad are critical. The experiments in this proposal are designed to find new pathways by which beta amyloid, the toxic peptide associated with ad, affects neurons in ad. In addition, new drugs will be tested to determine if they can reverse some of the detrimental effects of beta amyloid. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017033f name of organization or government: university of chicago. (h) purpose of grant: alzheimer's disease research by myles minter, phd entitled: (a2017044f) the role of microbial immune responses in alzheimer's disease. Investigator's summary: alzheimer's disease (ad) features brain deposition of amyloid-beta plaques and inflammation leading to dementia. Emerging evidence suggests that gut microbes (eg. Bacteria) can regulate the human immune system and influence brain function. This project will assess the role of gut microbes in regulating inflammation and amyloid-beta deposition in mouse models of ad. Knowledge gained will advance our understanding of ad pathogenesis, how gut microbes communicate with the brain, and potentially identify novel therapeutic targets. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017044f name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by randall bateman, md entitled: (a2017081s) in vivo stable isotope labeling & quantitative mass spectrometry imaging of a-beta plaque deposition in human alzheimer's disease. Investigator's summary: alzheimer's disease (ad) is a devastating neurological disease for which there is currently no effective therapeutics. Critical to the development of therapeutics that may treat and even cure ad is an understanding the dynamics (the change over time) of amyloid-beta (the likely cause of ad) in the human brain. We are using the most advanced imaging technology to answer these questions in patients in order to accelerate drug development and improve patient outcomes. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017081s name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by terrance kummer, md, phd entitled: (a2017084s) an mri fingerprint of synapse loss in alzheimer's disease. Investigator's summary: synapse loss is an early and invariant feature of alzheimer's disease (ad). The regional loss of synapses is among the strongest predictors of alzheimer's-induced cognitive decline. The development of a method to measure synaptic health regionally and longitudinally in human patients could have profound implications for understanding ad pathogenesis, and for monitoring the impact of therapies. Unfortunately, there is no well-validated method to measure regional synaptic density in vivo. Our prior work demonstrates the potential of diffusion mri approaches to reveal previously-unmeasured, disease-specific neural circuit breakdown. Loss of synaptic structures is known to alter water diffusion within neurons in ways amenable to diffusion mri analysis the objective of this proposal is to develop an mri fingerprint of synaptic density that can be used to longitudinally monitor regional synaptic health in mouse models and in humans with ad, and to connect changes in synaptic density with their functional consequences. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017084s”

“Name of organization or government: vanderbilt university. (h) purpose of grant: alzheimer's disease research by ethan lippmann, phd entitled: (a2017094s) high throughput discovery of blood-brain barrier functional components. Investigator's summary: in patients with alzheimer's disease and dementia, the blood vessels of the brain become leaky, which worsens symptoms like memory loss. We are trying to identify why these blood vessels become leaky -- if we understand the cause of this leakage, we can potentially target it with new drugs to improve patient outcomes. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017094s name of organization or government: johns hopkins university. (h) purpose of grant: alzheimer's disease research by resham chhabra, phd entitled: (a2017102f) depletion of tdp-43 as a risk factor to promote tauopathy in alzheimer's disease. Investigator's summary: the most important alteration in alzheimer's disease (ad) is the conformational change of a protein called tau, which then leads to the loss of brain cells and memory. Many studies have shown that another protein called tdp-43 is lost from the nucleus in 30-70% of ad cases and that these cases show worsened memory loss. The aim of our study is to find out if tdp-43 loss plays a role in changing the conformation of tau. Once we know what drives the changes in tau, we can halt or slow the progression of this disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017102f name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by sarah fritschi, phd entitled: (a2017114f) manipulating sleep/wake centers in alzheimer's disease-like mouse models. Investigator's summary: sleep problems such as wakefulness at night and daytime napping are common in patients with alzheimer's disease (ad) and are thought to manifest as a consequence of neurodegeneration. However, data suggest that sleep disturbances occur very early in the course of the disease and might not only be associated with ad but may precede the appearance of ad-associated pathologies, as well as the onset of cognitive symptoms. By switching sleep on and off we will be able to assess whether sleep disturbances such as unstable sleep, unusual sleep duration, sleep fragmentation and poor sleep quality are an early factor that contributes to the risk of developing ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017114f 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: (a2017144f) identification and validation of novel mapt splicing factors and rna-binding proteins. Investigator's summary: alzheimer's disease is part of a larger group of diseases that all result in the abnormal accumulation of a protein called 'tau' in the brain - these diseases are referred to as 'tauopathies.' there are six different versions of the tau protein in the human brain, and it is thought that an imbalance of the different versions result in their abnormal accumulation, and consequently, the development of a tauopathy. This project aims to discover what genes are responsible for regulating the different versions of tau so that we may better understand how and why an imbalance occurs, and what we could do to fix it. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017144f”

“Name of organization or government: beth israel deaconess medical center. (h) purpose of grant: alzheimer's disease research by tae ho lee, phd entitled: (a2017180s) identification of novel mechanisms in alzheimer's disease pathogenesis and progression. Investigator's summary: alzheimer's disease (ad) is the most common form of dementia, affecting millions people in the world but there is no effective therapy. Understanding molecular events leading to ad is vital for the development of new treatments. Our goal is to study the role of death-associated protein kinase 1 in ad using mouse models and to determine whether death-associated protein kinase 1 is important for neuronal cell death and the development of ad. This study would have a significant impact upon our basic understanding of ad, and might eventually lead the treatments of ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017180s name of organization or government: the j. David gladstone institutes. (h) purpose of grant: alzheimer's disease research by chaeyoung kim, phd entitled: (a2017214f) apolipoprotein e4: mitochondrial function and alzheimer's disease. Investigator's summary: apolipoprotein e (apoe) has important roles in both normal central nervous system (cns) physiology and neuropathology, such as alzheimer's disease (ad). Critical elements of ad pathology are mitochondrial dysfunction and metabolic impairment. Importantly, apoe4 generates toxic fragments that cause mitochondrial dysfunction and drive neurodegeneration; therefore, i will examine how apoe4 and its neurotoxic fragments interact with mitochondria and alter mitochondrial activity. This largely unexplored approach will provide insight into the mechanisms underlying apoe4 in ad and may identify new therapeutic targets by which to treat apoe4-associated ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017214f name of organization or government: vanderbilt university. (h) purpose of grant: alzheimer's disease research by richard darby, md entitled: (a2017226f) neurobiology of psychosis in alzheimer's disease. Investigator's summary: delusions and hallucinations commonly occur in alzheimer's disease, causing considerable distress for patients and families. The goal of this research is to determine why these symptoms arise using different types of brain scans and behavioral tests. Our hope is that understanding why delusions and hallucinations occur will help lead to new treatments for these symptoms in the future. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017226f. Name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by yi su, phd entitled: (a2017272s) blood brain barrier and metabolism in aging and alzheimer's disease. Investigator's summary: recently, vascular contributions to alzheimer's disease (ad) and dementia are increasingly recognized, but the exact role of neurovascular system in ad and dementia remains unclear. We hypothesize that changes to the neurovascular system underlie and contribute to the onset and progression of ad and dementia. In this project, we propose to use cutting-edge imaging techniques to measure these changes in vivo, and examine its relationship with aging and ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017272s”

“Name of organization or government: emory university. (h) purpose of grant: alzheimer's disease research by chadwick hales, md, phd entitled: (a2017281s) the role of ribonucleoprotein aggregate seeding in alzheimer's disease. Investigator's summary: brain cells are made up of many different proteins that help them work correctly. Bad proteins can build up in the brain cells and cause them to become sick and die in alzheimer's disease. We want to study how a group of these proteins causes bad proteins to build up in the cells. Results from the study may show us a new way to slow or stop the brain cell injury in alzheimer's disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017281s name of organization or government: harvard school of public health. (h) purpose of grant: alzheimer's disease research by majken jensen, phd entitled: (a2017290s) plasma fatty acids, antioxidants and alzheimer's risk. Investigator's summary: diet plays an important role in the development of many chronic diseases. However, we still don't have a good understanding of which dietary components are most important for the prevention of alzheimer's disease (ad). In this project we will identify key healthy dietary patterns that can form the foundation of dietary recommendations to lower risk of ad. This is important because diet is among the risk factors that are modifiable; thus we can change our behavior and lower our risk of this devastating disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017290s name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by yong wang, phd entitled: (a2017330s) pet-mri imaging of white matter damages and inflammation in alzheimer's disease. Investigator's summary: our new pet-mri method takes pictures of the brain in elderly people, which are commonly used to identify tumors or strokes in patients. We have found a new way to use pet-mri to measure the brain's injury and immune response. We previously found this to be very useful in patients with multiple sclerosis. Now we are able to use it in patients who have alzheimer's disease (ad), before they have memory problems, with a hope that this will be helpful to clinical trials testing new drugs for early intervention of ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017330s name of organization or government: emory university. (h) purpose of grant: alzheimer's disease research by jacki rorabaugh, phd entitled: (a2017345f) a new way of inhibiting tau propagation by modulating locus coeruleus physiology. Investigator's summary: abnormal forms of tau, an alzheimer's disease (ad)-associated protein, build up within the brainstem and eventually spread to other regions impairing function and contributing to memory loss. How and when tau spreads from the brainstem are unknown. Here we propose to examine how tau is transmitted from the brainstem to the forebrain in a rat model of ad. We hope that understanding tau spread may yield insights for new therapies and diagnostic tools for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017345f”

“Name of organization or government: ucla school of medicine. (h) purpose of grant: alzheimer's disease research by inma cobos, phd entitled: (a2017346s) a cell-type focused approach to define selective vulnerability in human alzheimer's disease brain. Investigator's summary: a close look at brain tissue from alzheimer's disease (ad) patients reveals that only some types of neurons have tau neurofibrillary tangles or others signs of neurodegeneration while others in close vicinity appear healthy. What makes some neurons more vulnerable or resistant to disease? We are using a new technique called "single cell rna sequencing" to isolate thousands of single neurons from human brain tissue, study all the genes that are expressed in each individual cell, and make cell-to-cell comparisons between normal, early stage and late stage ad. Our studies will clarify the precise identity of neurons involved by pathology and undergoing cell death in ad, and point to the main molecular pathways that confer vulnerability or resistance to disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017346s name of organization or government: university of chicago. (h) purpose of grant: alzheimer's disease research by pierre de rossi, phd entitled: (a2017366f) investigation of bin1 as a risk factor in tau pathology in an inducible transgenic model. Investigator's summary: genetic studies have recently uncovered several genes that can elevate the risk of developing alzheimer's disease (ad), including the bin1 gene as the second strongest genetic risk factor for late onset ad. My lab has generated a bin1 transgenic model to mimic the increase of bin1 protein in the brains of patients with ad. My goal is to use this transgenic mouse model to investigate how bin1 functions as a risk factor in ad. I expect that my proposed research will significantly advance the knowledge on bin1's function in the physiology of the brain, and reveal how it contributes to the disease pathology. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017366f name of organization or government: columbia university. (h) purpose of grant: alzheimer's disease research by karen duff, phd entitled: (a2017393s) tau propagation and proteasome mediated clearance. Investigator's summary: there is currently no cure for alzheimer's disease. We have identified a new way to treat the disease which is based on stimulating the brains own "garbage disposal units" to remove the toxic proteins that form clumps in the brain, which cause the memory loss. We wish to test how effective this treatment could be in a model of the disease and applying a drug we know can target the garbage disposal system of the brain. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017393s name of organization or government: the regents of the university of michigan. (h) purpose of grant: alzheimer's disease research by peter tessier, phd entitled: (a2017395s) peptide imaging agents specific for tau aggregates. Investigator's summary: alzheimer's disease (ad) is due to proteins that misbehave and stick together to form different types of protein particles that are toxic to brain cells. Early detection of this dreaded disease requires the generation of imaging molecules that can enter the brain and selectively tag toxic protein particles in different parts of the brain. We aim to use an innovative design and evolution method for generating imaging probes specific for particles of one of the most harmful alzheimer's proteins (tau). We will use these novel probes to image toxic protein particles in the brains of mice used as models of ad with the long-term goal of translating this technology to humans for early and accurate disease detection. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017395s”

“Name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by sarah devos, phd entitled: (a2017436f) in vivo monitoring and phenotyping of tau aggregation. Investigator's summary: a major driver of alzheimer's disease (ad) is the accumulation of the protein tau that travels through the human brain in a conserved pattern, though no one has yet identified how, or even if, these tau accumulations result in neuronal death. In this research, we have developed a fluorescent tool that will allow us to watch tau, aggregate in neurons in cell culture as well as neurons in the living adult mouse brain. Using this tool, this research aims to directly watch in real time what happens once a neuron develops an aggregate of tau as well as study what genes increase or decrease in a neuron once it develops one of these tau accumulations. Together, these data will help us better understand the immediate changes that occur in adult neurons when they develop ad-like tau accumulations and may help identify new drugable pathways involved in the development of ad in human patents. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017436f name of organization or government: university of chicago. (h) purpose of grant: alzheimer's disease research by angele parent, phd entitled: (a2017443s) membrane-targeted aicd: effect on cognition and a-beta. Investigator's summary: for the past two decades, researchers in alzheimer's disease (ad) field have focused on the neurotoxicity associated with amyloid-beta (a-beta) peptide production and accumulation; a small peptide generated from cleavage of amyloid precursor protein (app). Our studies will explore the app molecule as a whole cellular component that could affect brain function and memory process. We will test the hypothesis that production of the intracellular fragment originating from app could rescue memory decline in ad mice models. Viral injection in the brains of these mice will facilitate the overproduction of this fragment. Our investigations will provide us with a more meaningful understanding of how targeting app intracellular domain at the membrane could reduce cognitive decline and benefit ad patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017443s name of organization or government: wake forest school of medicine. (h) purpose of grant: alzheimer's disease research by tao ma, phd entitled: (a2017457s) role of eef2 hyper-phosphorylation in alzheimer's disease-associated synaptic failure and memory deficits. Investigator's summary: the basic causes underlying the cognitive deterioration in alzheimer's disease (ad) and other dementias remain elusive, which hampers development of any effective therapies. This project will help understand the role of new protein synthesis associated with eef2k/eef2 signaling in ad pathogenesis. This work could inform future identification of novel diagnostic markers and therapeutic targets for ad and related cognitive syndromes. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017457s name of organization or government: icahn school of medicine at mount sinai. (h) purpose of grant: alzheimer's disease research by edoardo marcora, phd entitled: (a2017458s) understanding the role of apolipoprotein e in microglia. Investigator's summary: human genetic studies strongly point to apolipoprotein e (apoe) and microglia (the immune cells of the brain) as, respectively, the most important gene and cell type in the chain of events that leads to alzheimer's disease (ad), a common disorder in the elderly in which the brain is damaged and memories falter. In normal conditions, microglial cells do not make apoe; however, in disease conditions, they sense the brain damage and respond by churning out apoe. It is unclear why this occurs and the goal of this project is to answer this question by investigating what happens”

“Name of organization or government: cornell university. (h) purpose of grant: alzheimer's disease research by chris schaffer, phd entitled: (a2017488s) blocking neutrophil adhesion to improve brain blood flow in alzheimer's disease. Investigator's summary: blood flow to the brain is reduced by about one-third in alzheimer's disease (ad) patients and this blood flow reduction contributes to the memory problems of the disease. In mice models of ad, we have recently discovered that the blood flow reduction is due to white blood cells that get stuck and block blood flow in the smallest blood vessels, individual brain capillaries. When we eliminated these capillary stalls, the alzheimer mice showed a 30% increase in brain blood flow as well as improved performance on memory tasks. Here we propose to screen drugs that interfere with white blood cell adhesion and that have already been proven to be safe in humans to find compounds that reduce capillary stalling and could be tried in ad patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017488s name of organization or government: georgetown university. (h) purpose of grant: alzheimer's disease research by daniel pak, phd entitled: (a2017508s) evaluating plk2 for alzheimer's disease therapy. Investigator's summary: alzheimer's disease is thought to be due to the build-up of a substance in the brain called a-beta. Although the basic process that generates a-beta is well studied, an important unresolved question is what factors turn this process on and off. We have identified for the first time plk2 as a candidate factor that stimulates a-beta production, and here we will examine the role of plk2 in disease progression using mouse models of alzheimer's. These studies are critical for understanding the mechanisms underlying alzheimer's and for advancing new targets for drug therapies. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017508s name of organization or government: pennington biomedical research center. (h) purpose of grant: alzheimer's disease research by robert newton, phd entitled: (a2017547s) exercise intervention to reduce risk of alzheimer's disease in african americans. Investigator's summary: this study will determine if we can get elderly african american adults to exercise more. If we do, we believe that we can improve their thinking and hopefully prevent them from developing thinking problems as they get older. Many elderly people have problems in their thinking, also known as dementia, and we hope to reduce people's risk of developing dementia. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017547s name of organization or government: university of california, berkeley. (h) purpose of grant: alzheimer's disease research by jin rui liang, phd entitled: (a2017557f) identification of novel er-phagy proteins that are implicated in neurodegeneration. Investigator's summary: my project aims to discover the key proteins that are involved in the degradation of endoplasmic reticulum (er) via a process called er-phagy. Recently, multiple reports have shown that defects in this process could potentially lead to neuronal defects and neurodegenerations, including alzheimer's disease. However, not much is known with regards to the proteins and the regulation process of er-phagy. My project aims to establish the link between these erphagy-related proteins with neurodegeneration. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017557f”

“Name of organization or government: university of california, san francisco. (h) purpose of grant: alzheimer's disease research by lea grinberg, md, phd entitled: (a2017560s) diagnosing and monitoring prodromal alzheimer's disease using novel locus ceruleus-based imaging volumetry. Investigator's summary: it would be extremely useful for drug trials, screening purposes and clinical management, to be able to monitor alzheimer's disease (ad) pathological progression, especially during the decades preceding the onset of clinical symptoms when the disease spreads silently in the brain. To date, postmortem examination remains the only tool to confirm and stage ad diagnosis. We found that a tiny brainstem nucleus, the locus ceruleus (lc) is especially vulnerable and earliest-damaged in ad. Furthermore, investigating postmortem tissue, we found evidence that in ad patients, lc showed linear and progressive shrinkage. We will develop a histologically-validated clinical mri template for detecting lc shrinkage to track individuals' ad progression, that might permit intervention before a substantial amount of neurons have died. Lc volumetry is potentially more scalable and economical than other potential ad biomarkers, and could be developed for longitudinal screening to help select high-risk candidates for less accessible, more expensive and more invasive studies (e.g. Pet scan; spinal taps). For more information, visit the brightfocus website: www.brightfocus.org/grant/a2017560s name of organization or government: c2n diagnostics, llc. (h) purpose of grant: alzheimer's disease research by philip verghese, phd entitled: (ca2016636) silk alpha-beta spot test. Investigator's summary: alzheimer disease (ad) is the most common cause of dementia and currently affects more than 5 million people in the usa alone, with millions more at high risk. Ad deprives people of their memories, independence, and functional capacity. The quality of rational drug development in ad has suffered from the absence of relevant and simple dynamic biomarkers. Dynamic biomarkers can be essential for selecting patients in studies who are most likely to benefit from therapy. Such biomarkers can help validate drug action, eliminate undeserving drug candidates early, and optimize dosing and scheduling to maximize future chances of clinical drug development success. A dynamic marker also can assist in monitoring drug activity in pre-symptomatic patients. It can track the therapeutic responsiveness of individual patients, predict clinical benefit, and follow disease progression. As of today, no simple dynamic biomarker for ad exists. C2n diagnostics has unique and novel platforms, termed stable isotope labeling kinetics (silk) and stable isotope spike absolute quantification (sisaq), that measure the metabolism and abundance of brain-derived biomolecules implicated in ad and other forms of neurodegeneration. The primary objective of c2n's brightfocus award is to develop novel and simple blood tests using the silk and sisaq platforms that can be used for 1) aiding in selection of patients for inclusion in ad trials, 2) demonstrating drug target engagement, and 3) tracking disease progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2016636 name of organization or government: anthrotronix, inc. (h) purpose of grant: alzheimer's disease research by corinna e. Lathan, phd, pe entitled: (ca2016602) health ebrain study ii: addressing depression and cognitive functioning in dementia caregivers. Investigator's summary: the health-ebrain study seeks to understand the cognitive functioning of dementia caregivers who are heavily burdened and who are at risk for mood disorders. This virtual longitudinal study is comprised of an intervention case management arm and a waitlist control arm. Additionally participants may be selected to participate in a cognitive wellness group where their cognition is solely tracked over time using the dana brain”

“Name of organization or government: human computation institute. (h) purpose of grant: alzheimer's disease research by pietro michelucci, phd entitled: (ca2016629) crowd-powered microvascular modeling. For more information, visit the brightfocus website: www.brightfocus.org/grant/ca2016629 name of organization or government: university of nebraska medical center. (h) purpose of grant: national glaucoma research by matthew van hook, phd entitled: (g2017027) early melanopsin ganglion cell dysfunction in glaucoma. Investigator's summary: glaucoma is disease often associated with increased pressure in the eye that causes blindness when the nerve cells (called retinal ganglion cells, or rgcs) carrying information from the eye to the brain die. One particular group of rgcs, called melanopsin rgcs, plays critical roles in regulating of sleep, mood, and pupil constriction and it is likely that their function is altered during glaucoma. This project seeks to determine how melanopsin rgc performance and signaling to the brain are altered at early stages of glaucoma, after increases in eye pressure but before rgcs die. This will help doctors understand some of the earliest signs of glaucoma and develop ways to detect the disease at its earliest stages and prevent blindness. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017027 name of organization or government: johns hopkins university. (h) purpose of grant: national glaucoma research by fengquan zhou, phd entitled: (g2017037) reprogramming retinal ganglion cells for axon regeneration. Investigator's summary: the proposed study aims to study two novel approaches for promoting long distance optic nerve regeneration. Based on our completed genetic study, we will first test if pharmacological inhibition of the identified protein via direct eye injection can promote long distance optic nerve regeneration. Based on strong preliminary data, we will determine if manipulation of another novel gene can induce long distance optic nerve regeneration. The project will not only identify a potential translational approach for promoting optic nerve regeneration, but also open a new avenue for identifying novel gene targets that can be manipulated to enhance optic nerve regeneration. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017037 name of organization or government: boston medical center. (h) purpose of grant: national glaucoma research by ji yi, phd entitled: (g2017077) exploration of optical markers for glaucoma early detection. Investigator's summary: glaucoma is an eye disease that affects millions of american's vision. The best way to slow and stop the disease is to detect it early; however, existing methods are insufficient to do so. We plan to develop a new optical imaging technology to examine the eye, which is very sensitive to early glaucoma so that we can use it for early diagnosis. This project not only may benefit many people by preventing their blindness, but also could enhance our understanding in how this disease develops. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017077”

“Name of organization or government: university of pittsburgh. (h) purpose of grant: national glaucoma research by ethan rossi, phd entitled: (g2017082) in vivo imaging of individual retinal ganglion cells in glaucoma. Investigator's summary: vision loss in glaucoma is due to the death of a type of nerve cell in the eye that is nearly transparent and that has proven very difficult to image. We recently devised a way to see these cells in the living eye. Our project will improve this tool and develop a new one that we will use to look at these cells in people with glaucoma for the first time. This will allow us to see the earliest changes to these cells, track how they change over time and monitor their response to treatments. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017082 name of organization or government: the schepens eye research institute. (h) purpose of grant: national glaucoma research by tobias elze, phd entitled: (g2017111) computational investigation of glaucoma progression. Investigator's summary: glaucoma is accompanied by typical functional vision loss, so-called visual field defects, which may progress over time, which is why visual fields of glaucoma patients are regularly measured. However, these measurements are noisy, and it is often hard for clinical practitioners to decide whether changes over time reflect true changes of functional vision or are the result of normal measurement variations or artifacts. The aim of this project is to investigate the spatial configuration of glaucomatous visual field defects by a combination of mathematical algorithms and clinical expertise and to identify patterns of disease progression. The resulting quantitative models will be implemented as a software which calculates, for a given patient measurement of the probability of if, how, and how quickly vision loss is expected to progress. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017111 name of organization or government: university of california, san diego. (h) purpose of grant: national glaucoma research by linda zangwill, phd entitled: (g2017122) the role of microvasculature in the pathophysiology of glaucoma. Investigator's summary: numerous studies have suggested that vascular factors (blood supply) are involved in the development of glaucoma, but it is currently not known whether a reduction in blood supply to the eye is a cause or an effect of the glaucoma disease process. Recent advances in imaging technology have made visualization and measurement of the retinal blood supply possible during routine eye exams. This prospective clinical research study will investigate whether changes in the retinal blood supply precede or follow other structural and mechanical changes in glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017122 name of organization or government: university of north texas health science center. (h) purpose of grant: national glaucoma research by weiming mao, phd entitled: (g2017151) crispr interference-mediated inhibition of tgf beta 2 in the trabecular meshwork. Investigator's summary: the most important risk factor and treatment target of glaucoma is elevated pressure inside the eye. Current drugs that lower eye pressure do not treat the pathology of glaucoma, and therefore they tend to lose effect after prolonged treatment. Many studies showed that high levels of tgf beta 2 causes high eye pressure. Our proposed study aim to use a novel technology called crispr interference to correct those abnormal protein modifications and return the high tgf beta 2 level to normal. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017151”

“Name of organization or government: the jackson laboratory. (h) purpose of grant: national glaucoma research by krish kizhatil, phd entitled: (g2017152) determining the neuronal control of intraocular pressure. Investigator's summary: glaucoma is a devastating neurodegenerative disease that causes blindness. Glaucoma results from increased pressure in the eye, however the mechanistic basis of the pressure increase is largely undetermined. Neurons innervating the eye play a role in controlling pressure but again the specific mechanisms are not clear. We will determine the mechanistic basis of neuronal control of eye pressure suing mice and modern imaging and molecular methods. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017152 name of organization or government: devers eye insitute. (h) purpose of grant: national glaucoma research by brad fortune, od, phd entitled: (g2017170) early-stage axon damage: active transport and cytoskeletal ultrastructure within individual axons of glaucomatous non-human primate eyes. Investigator's summary: current clinical gold-standard methods for assessing the structural integrity of nerve fibers damaged by glaucoma are only able to detect complete loss of those fibers from the retinal layer within the eye where they are normally located. By the time such loss is detected, it is too late to rescue those fibers or the signals about vision they had previously carried to the brain. In order to prevent loss of those fibers and the vision they carry, more sensitive techniques are needed to detect subtler abnormalities that occur at an earlier stage of injury from glaucoma. We seek in this proposal to determine whether a particular type of imaging is capable of reporting on the integrity of sub-microscopic structures within optic nerve fibers at an early stage of damage preceding their complete degeneration and loss from the eye. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017170 name of organization or government: michigan state university. (h) purpose of grant: national glaucoma research by andras komaromy, dvm, phd entitled: (g2017185) gene therapy in canine primary open angle glaucoma. Investigator's summary: glaucoma is a progressive disease that targets a specific type of neuron in the retina call the "retinal ganglion cell". The loss of these cells causes blindness. While glaucoma is associated with elevated pressure within the eye, lowering this pressure will only delay development of glaucoma. Eventually, the disease will continue to progress even though the pressure within the eye is lowered. This research project will test a new form of treatment for glaucoma that uses a novel gene therapy approach to protect retinal neurons and stop glaucoma from developing, even in the presence of elevated intraocular pressure. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017185 name of organization or government: university of north texas health science center. (h) purpose of grant: national glaucoma research by gulab zode, phd entitled: (g2017199) targeting er stress for the treatment of steroid and myocilin glaucoma. Investigator's summary: elevation of eye pressure can lead to blindness in humans. The trabecular meshwork tissue, which controls eye pressure, is damaged in glaucoma, thus raising eye pressure. Our recent work identified that endoplasmic reticulum stress to the trabecular meshwork cells is involved in elevation of eye pressure. Specifically, we discovered that two molecules atf4 and chop are involved in this process. In this proposal, we will test whether inhibition of these molecules, via new drug, lowers eye pressure using mice and cultured trabecular meshwork cells. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017199”

“Name of organization or government: university of connecticut health center. (h) purpose of grant: national glaucoma research by feliks (ephraim) trakhtenberg, phd entitled: (g2017204) the molecular mechanisms of retinal ganglion cell axon growth and regeneration. Investigator's summary: the biological molecular mechanisms controlling the growth of connections in the central nervous system are still poorly understood. The inability of the eye to regenerate such connections to the brain is the key reason why vision lost after damage to the optic nerve in a disease such as glaucoma cannot be restored. We propose to identify novel biological regulators of the intrinsic ability of the retinal cells for regrowing such connections between the eye and the brain. These studies could lead to the development of therapeutics for restoring simple visual abilities to those who became blind due to angle-closure glaucoma and possibly other types of glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017204 name of organization or government: university of california, san diego. (h) purpose of grant: national glaucoma research by derek welsbie, md, phd entitled: (g2017212) novel aav/crispr therapeutic for dlk inhibition. Investigator's summary: nerve cells called retinal ganglion cells form the connection between the eye and the brain. In glaucoma, these nerve cells die and vision is permanently lost. We have previously shown that a protein called dual leucine zipper kinase (dlk) is critical for the death of these cells. Thus, this proposal seeks to develop a gene therapy vector that might interfere with dlk and prevent retinal ganglion cell death. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017212 name of organization or government: university of california, san francisco. (h) purpose of grant: national glaucoma research by douglas gould, phd entitled: (g2017218) testing lens-derived signaling pathways in ocular dysgenesis. Investigator's summary: normal eye development is a complex process that is poorly understood. People with small developmental defects in the front of the eye are at very high risk of going blind as children or young adults. We are studying genes involved in normal eye development so that we may understand how defects lead to blindness and if there are ways to intervene and prevent vision loss. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2017218 name of organization or government: university of california, san diego. (h) purpose of grant: macular degeneration research by daniel chao, md, phd entitled: (m2017034) characterization of a zebrafish model of wet macular degeneration. Investigator's summary: the purpose of this study is to develop a new model of wet macular degeneration using zebrafish, a common pet store fish. The advantages of zebrafish are that they are small, inexpensive, have retinas very similar to humans, and can be used for large scale drug screens. We have characterized a particular zebrafish strain which has growth of abnormal vessels in the retina, very similar to what happens in wet amd. We will perform drug screens in this zebrafish to identify drugs which inhibit abnormal blood vessel growth, and may show promise as therapeutics for macular degeneration. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017034”

“Name of organization or government: university of florida. (h) purpose of grant: macular degeneration research by astra dinculescu, phd entitled: (m2017035) the role of basal c1qtnf5-s163r mutant deposits in drusen formation: implications for amd. Investigator's summary: age-related macular degeneration (amd) is a multifactorial disease that causes blindness in the elderly population. It is characterized by the presence of abnormal, thick extracellular deposits that block the nutrients and oxygen to the photoreceptors in the eye, causing vision loss. This proposal is based on the idea that these deposits are a result of multiple, simultaneous stressors that lead to cell death. Our goal is to understand the formation and molecular composition of these extracellular deposits, in order to develop a strategy to eliminate them, and preserve vision in human patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017035 name of organization or government: the jackson laboratory. (h) purpose of grant: macular degeneration research by patsy nishina, phd entitled: (m2017042) the role of the extracellular matrix in posterior eye diseases. Investigator's summary: genes are made up of precise building blocks (i.e. Imagine square blocks stacked together in an orderly fashion). Sometimes there are differences in these building blocks between people, some may cause disease (i.e. Shaped liked a triangle rather than square, causing the stack to be unstable) but others may just be a benign change (i.e. Color change from red to orange). Our goal is to determine which change is disease causing and then to take that variant and create a mouse model that carries the disease causing change. This mouse model then can be used to study what the change in building block does in the eye, how it leads to disease, and it can also be used to test different treatments. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017042 name of organization or government: johns hopkins university. (h) purpose of grant: macular degeneration research by michael paulaitis, phd entitled: (m2017060) rote of exosomal mirnas in rpe cell mitochondrial dysfunction in early amd. Investigator's summary: retinal physicians have witnessed the detrimental impact of vision loss on age-related macular degeneration (amd) patients. The decrease in quality of life from early amd is similar to that caused by hiv, and with advanced amd, of metastatic prostate cancer with uncontrollable pain. Due to these visual changes in early amd, patients have as much anxiety from the threat of losing vision as they do from being blind, in part, because there is no treatment to halt or restore vision in amd. The novel concepts put forth in this study of small molecules called "micrornas and what they can tell us about mitochondria disorders in cells of the retina hold great promise of discovering new insights into how amd develops upon which new treatments can be designed to save or improve vision. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017060 name of organization or government: university of utah. (h) purpose of grant: macular degeneration research by binxing li, phd entitled: (m2017066) mechanism of sr-bi-mediated macular carotenoid transport. Investigator's summary: supplementation of macular carotenoids can protect human retina against age-related macular degeneration (amd), a leading cause of blindness in u.s. However, the relevant mechanism of macular carotenoid transport is still remain unknown because there has been no appropriate small animal capable of accumulating carotenoid in their retinas. More recently, we discovered that mice deficient in bco2, a carotenoid cleavage enzyme, can deposit carotenoid in their retinas, and we plan to use this mouse model to study the biochemical mechanism underlying macular carotenoid transport mediated by sr-bi, a critical carotenoid transporter. The res”

“Name of organization or government: university of massachusetts school of medicine. (h) purpose of grant: macular degeneration research by claudio punzo, phd entitled: (m2017071) role of photoreceptors in amd. Investigator's summary: age-related macular degeneration (amd) is one of the leading causes for blindness in the elderly population of the industrialized world. Besides aging of the body, what causes the disease to occur in a certain percentage of elderly people is not understood, which makes it difficult to develop therapeutic strategies. Based on a new paradigm shifting idea on how amd develops, we have generated a new mouse model for the disease that for the first time shows a natural progression of most of the clinical pathologies found in humans including geographic atrophy and wet amd. Our new mouse model of amd allows us, for the first time, to study how amd develops, which will help us with the development of new rational therapeutic approaches. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017071 name of organization or government: oregon health and science university. (h) purpose of grant: macular degeneration research by trevor mcgill, phd entitled: (m2017073) characterization of the relationships among a2e, lipofuscin, and macular pigments in a primate model of amd. Investigator's summary: age-related macular degeneration (amd) is the most common cause of legal blindness in the elderly in developed countries and a leading cause of blindness worldwide. The typical american diet is low in nutritional factors that may reduce the risk or severity of amd. The goal of this project is to determine the consequences of deprivation of these nutrients on the development of age-related retinal disease, and determine the mechanisms by which this occurs. The results of these studies will provide direct evidence for the importance of these nutritional factors in maintaining retinal health and preventing advanced retinal disease, and may reveal new options for therapeutic intervention. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017073 name of organization or government: university of miami, miller school of medicine. (h) purpose of grant: macular degeneration research by gaofeng wang, phd entitled: (m2017081) epigenetic prevention of amd progression by vitamin c. Investigator's summary: currently, the first line treatments for wet age related macular degeneration (amd) is to block the function of vegf, a major factor promoting the growth of new blood vessels in the eye. Besides the high costs, these treatments need injections into the eyeball using syringes, which is complicated and can be dangerous. Based on a novel finding of ascorbate (vitamin c) in regulating the function of the genome from our lab, this research plans to inhibit the production of vegf in the eye, thus blocking its function. Successful completion of this research will help develop an ascorbate treatment, which is inexpensive and readily available, for amd patients to delay and/or prevent disease progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017081 name of organization or government: university of florida. (h) purpose of grant: macular degeneration research by cristhian ildefonso, phd entitled: (m2017126) local and systemic inflammation in a mouse model of rpe-oxidative damage. Investigator's summary: macular degeneration is a leading cause of blindness among the older population of the united states of america and other developed countries. Inflammation has been linked to age-related macular degeneration. My research goal is to improve a mouse model of this disease by introducing pro-inflammatory cues, and to test a method of decreasing inflammation in the eye to test the idea that localized control of inflammation could help protect vision. If successful, this method could also be tested in other diseases linked to aging and inflammat”

“Name of organization or government: tufts university. (h) purpose of grant: macular degeneration research by sheldon rowan, phd entitled: (m2017147) role of the gut microbiota in a mouse model of amd. Investigator's summary: we understand now that most of the risk for developing age-related macular degeneration (amd) comes from environmental causes, particularly our diets and nutrition. However, we don't know why these dietary factors change the risk of amd or how they affect our bodies. One possibility is that our diets are actually affecting the composition and function of the micro-organisms that live within our body, particularly our guts, collectively known as the microbiome. This proposal will directly test the idea that bacteria in our guts alter the likelihood and degree to which mice fed a poor diet develop amd by either killing bacteria with antibiotics, or moving them from one mouse to another. We will not only evaluate the eye for disease, but also measure a large number of molecules in the urine that may be used as a foundation for future medical tests for amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017147 name of organization or government: boston children's hospital, harvard medical school. (h) purpose of grant: macular degeneration research by jing chen, phd entitled: (m2017161) targeting rev-erb alpha to preserve rpe/photoreceptor in amd. Investigator's summary: age-related macular degeneration (amd) is a major cause of irreversible vision loss in the elderly resulting from death of cells critical for vision: retinal pigment epithelial cells (rpe) and photoreceptor cells. Currently there is no treatment to prevent or slow the loss of these cells in dry amd patients. This work aims to investigate mechanistically the molecular processes through which dysregulation of oxidative stress impairs rpe and photoreceptor cellular metabolism and their survival in amd. Novel activators of this molecular pathway will be evaluated in a pre-clinical animal model of amd to determine if treatment is effective in preventing or slowing the development of amd-like pathologies. Findings from this work will identify a novel drug target for developing potential therapies for preventing cell death and preserving vision in dry amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017161 name of organization or government: tufts university. (h) purpose of grant: macular degeneration research by rajendra kumar-singh, phd entitled: (m2017175) role of complement and therapy for amd. Investigator's summary: a part of the immune system known as complement is known to be activated and is the underlying cause of age-related macular degeneration (amd) in a very significant portion of amd patients. Although there are many animal models of amd, there are almost none that exhibit disease similar to that of humans specifically because of activation of the complement system. We have recently developed such an animal model and here we propose to use this model to study the role of complement in amd as well as develop a gene therapy for amd. Upon completion of these studies we will have a better understanding of the role of complement in amd as well as have proof of principle for a gene therapy for amd--information that is necessary towards preclinical safety testing and product development for an amd therapy in humans. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017175 name of organization or government: duke university eye center. (h) purpose of grant: macular degeneration research by daniel saban, phd entitled: (m2017183) role of bona fide microglia in retinal degeneration. Investigator's summary: the deterioration of light-sensing nerves of the retina contributes to vision loss in patients with age-related macular degeneration. The immune system is thought to contribute to this deterioration, but how this is accomplished remains elusive.”

“Name of organization or government: the university of texas medical branch at galveston. (h) purpose of grant: macular degeneration research by yan chen, phd entitled: (m2017186) metabolic regulation by mechanistic target of rapamycin in the retinal pigment epithelium. Investigator's summary: every morning when we open our eyes to see the world around us, the neurons in our retina begin to work. Their intense work load demands high energy. The retinal neurons rely on their supporting cells, such as retinal pigment epithelium, to provide them with the energy fuel. In this project we will study the mechanisms of energy production and regulation, in both healthy and diseased eyes. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017186 name of organization or government: stanford university. (h) purpose of grant: macular degeneration research by philippe mourrain, phd entitled: (m2017209) deeply conserved gwas snps reveal a regulatory mutation underlying amd. Investigator's summary: age-related macular degeneration (amd) is one of the leading causes of blindness in the world but its genetics is still unclear. Most of the dna variations identified in amd patients are found outside of the genes and it is extremely hard to know whether these variants are actual mutations and what genes they affect. We have found that some of these variants are located in genome regions conserved down to the zebrafish and surrounded by the same neighborhood of genes. This conservation allows us to visualize in this transparent genetic vertebrate model whether these variants are just neutral or if they disrupt the regulation of one the neighbor genes, thus revealing the actual gene affected in amd human patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2017209 name of organization or government: helen keller foundation for research & education. (h) purpose of grant: macular degeneration research by entitled: helen keller prize for vision research partnership. Summary: the helen keller prize for vision research recognizes significant accompishments in vision research, and provides funds for continuance of those studies.”