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 (brightfocus) seeks to save mind and sight by funding innovative research worldwide and by promoting better health through education. We focus our efforts on three incurable diseases affecting mind and sight: alzheimer's disease, macular degeneration, and glaucoma. Collectively, 1 in 16 people over the age of 40 in the u.s. Alone 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 $150 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. 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 2016, these psa messages generated $13,318,687 in donated media services and garnered 1.3 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 "snapshot" series graphically communicates information on alzheimer's, macular degeneration, and glaucoma. Through our social media and web resources, we conduct contests and promotions to increase”

“Recoveries of prior year grants 29,516. Change in present value of grants 33,085.”

“Region: europe (d) purpose of grant: alzheimer's disease research by patrick kehoe, bsc, phd entitled: (a2016582s) exploring ace-2 as a novel therapeutic target for alzheimer's disease. Investigator's summary: the renin-angiotensin system (ras) is a biochemical pathway primarily involved in blood pressure regulation, but which becomes overactive in alzheimer's disease (ad). Previous research has shown that some commonly prescribed anti-hypertensive drugs that also work in the ras system can protect against rates of alzheimer's in people, and also against cell and brain tissue damage, as well as cognitive decline, in animal models of ad. We have just found that an important regulatory arm of ras is also defective in ad and that reduced activity of this pathway is associated with more extensive pathology in human brain tissue. Our proposed study will investigate whether activation and enhancement of this regulatory pathway, using a drug already available for testing in people but previously not considered in ad, can protect against both cognitive decline and tissue damage normally seen in an established mouse model of ad, potentially resulting in a new therapy that can move rapidly to clinical trial testing for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016582s. Grant awarded: $300,000, university of bristol, bristol, united kingdom. Region: europe (d) purpose of grant: national glaucoma research by rudolf fuchshofer, phd entitled: (g2016076) role of non-coding rnas in outflow resistance dysregulation. Investigator's summary: lowering of intraocular pressure (iop) in glaucomatous patients slows or stops progression of damage to their optic nerve. The pathology responsible for the elevated iop associated with glaucoma lies in the conventional aqueous humor outflow pathway. Somewhat remarkably, no current pharmacological therapy for glaucoma is directed at this pathway. The proposal focuses on the functional role of non-coding rnas on the nitric oxide system and their potential involvement in regulation of the conventional outflow pathway. The investigation could lead to a new therapeutic approach that would be additive to current therapies and thereby useful in stabilizing disease progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016076. Grant awarded: $149,596, university of regensburg, regensburg, germany. Region: europe (d) purpose of grant: macular degeneration disease research by sarah doyle, phd entitled: (m2016030) the role of toll/il-1 receptor (tir)-signaling "checkpoint" regulators in pathobiology of amd. Investigator's summary: the inflammatory response is needed to take care of all the tissues that make up our body to keep us in working order. However, inflammation is a double-edged sword, too much can cause damage to the surrounding tissues, too little can be ineffective at inducing healing. To overcome this problem, the inflammatory response has evolved so that once a pro-inflammatory response is generated, it promotes the expression of chemicals that provide feedback and switch off inflammation by inhibiting the very pro-inflammatory signals that generated them; in this way, the process of inflammation programs its own end. Amd has elements that indicate that the inflammatory response is uncontrolled and persistent low-level inflammation is observed. Our research question asks whether this active process of switching off the inflammatory response is lost in people with amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016030. Grant awarded: $160,000, trinity college dublin, dublin, ireland. Region: east asia & pacific (d) purpose of grant: macular degeneration disease research by robyn guymer, phd entitled: (m2016061) failure to remove debris: defective mechanisms may play a role in the pathogenesis of amd. Investigator's summary: understanding the underlying mechanisms by which debris accumulat”

“Region: east asia & pacific (d) purpose of grant: macular degeneration disease research by paul baird, bsc, phd entitled: (m2016178) identifying gene pathways that delineate the two late stage types of disease in amd. Investigator's summary: there are two types of blinding age-related macular degeneration (amd) but treatment is only currently available for one of these. We have developed a novel statistical tool and high throughput computational model that allows us to look at all genes in our genome and identify those genes that interact with each other to cause both of these types of amd. Using the world's largest collection of amd samples, drawn from multiple cohorts of 40,000 people, we will identify the important genetic interactions in each type of amd. Using this knowledge, we will be able to better understand the disease process and develop new therapies allowing both types of blinding amd to be treated. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016178. Grant awarded: $80,000, centre for eye research, melbourne, australia. Region: north america (d) purpose of grant: macular degeneration disease research by brian ballios, md, ph.d. Entitled: (m2016173) bioengineered stem cell-derived cone photoreceptor therapy. Investigator's summary: drug therapy only slows the progression of disease, but does not represent a regenerative approach to macular degeneration treatment. We will use stem cells to produce large quantities of cone photoreceptors for transplantation directly into the retina. Cones are the cells responsible for high-resolution/color vision and are lost in disease. We will take advantage of natural biomaterials as vehicles to deliver cells to the eye, to increase their survival and improve their function after transplantation. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016173. Grant awarded: $160,000, university of toronto, toronto, canada.”

“Name of organization or government: johns hopkins university. (h) purpose of grant: alzheimer's disease research by jason brandt, phd entitled: (a2016073s) modified atkins diet for cognitive loss in older adults. Investigator's summary: this study will test whether a special diet that has been used to treat other brain disorders may be useful to treat alzheimer's disease (ad). The diet is very low in starches and sugars, and very high in fat. Such a diet causes the body to produce substances called "ketones" which can be used by the brain for energy. This study will test whether patients with early ad, or even milder memory problems known as mild cognitive impairment (mci), can stick to this diet for 12 weeks and whether it improves their thinking and memory. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016073s name of organization or government: case western reserve university. (h) purpose of grant: alzheimer's disease research by jiri safar, md entitled: (a2016085s) profiling structure and biology of beta amyloid strains. Investigator's summary: we believe our application addresses a confounding puzzle: why clinical symptomatology, severity, and progression rates of late-onset alzheimer disease (ad) frequently do not coincide with the total amyloid-beta (a-beta) load. We propose to test the hypothesis that rapid progression of the disease is caused by specific molecular structural features of beta amyloid. The findings have a potential to significantly improve our understanding of ad and to establish progression rate-directed diagnostics and therapeutic interventions as a key strategy for delaying and preventing symptomatic ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016085s name of organization or government: baylor college of medicine. (h) purpose of grant: alzheimer's disease research by huda zoghbi, md entitled: (a2016151s) genetic screens to identify targets that regulate app. Investigator's summary: alzheimer disease (ad) is characterized by the deposition of amyloid plaques and the accumulation of neurofibrillary tangles, products of amyloid precursor protein (app) processing and tau hyperphosphorylation respectively. Several studies demonstrate that reduction of app is therapeutically beneficial in ad mouse models. This evidence prompted us to hypothesize that modest reduction in the levels of app proteins would delay the onset and retard progression of disease. We plan to identify new therapeutic targets using an unbiased, high-throughput screen using two different assay systems in parallel (human neuronal cell lines and fruit flies expressing human app) to identify those proteins whose reduction results in lower levels of app, and rescues neuronal degeneration in flies. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016151s name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by iman aganj, phd entitled: (a2016172s) connectomic biomarkers of alzheimer's disease observed in multi-synaptic pathways. Investigator's summary: the human brain consists of complex structural and functional networks. Network-based analysis of brain white matter connections has proved promising by helping to reveal the structural basis of alzheimer's disease (ad), and assisting in the discovery of diagnostically and therapeutically important biomarkers. The goal of the proposed project is to build on the investigator's background in brain imaging and brain network analysis to develop and validate novel computational methods such as those accounting for indirect neural pathways and subsequently derive more accurate ad imaging biomarkers, which will help us better understand how the brain is affected in alzheimer's disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016172s”

“Name of organization or government: washington university school of medicine. (h) purpose of grant: alzheimer's disease research by brendan lucey, md entitled: (a2016180s) sleep quality and human amyloid-beta kinetics. Investigator's summary: the deposition of amyloid-beta protein (a-beta) in the brain is a key first step in alzheimer's disease (ad). Recent work has shown that sleep decreases the concentration of a-beta in the brains of mice and humans. In mice, decreasing the amount of sleep both reduced the a-beta concentration and deposition in the brain suggesting that sleep could be a therapy to prevent ad. Key questions remain, however, before ad prevention trials using sleep can begin. This study proposes to answer several of these questions: 1) does poor sleep quality increase a-beta and 2) does improving sleep quality in poor sleepers decrease a-beta? For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016180s name of organization or government: university of california, san diego. (h) purpose of grant: alzheimer's disease research by emilie reas, phd entitled: (a2016241f) microstructural markers of cognitive aging and mild cognitive impairment. Investigator's summary: as age-related cognitive impairment and dementia are growing health concerns for our aging population, it's becoming increasingly important to develop tools to accurately detect the earliest signs of alzheimer's disease (ad). Although imaging methods, such as magnetic resonance imaging (mri), have shown promise at measuring changes in brain structure associated with cognitive impairment and dementia, these approaches are relatively insensitive to the earliest disease stages, when treatments will likely be most effective. A new brain imaging technique, restriction spectrum imaging (rsi), has shown promise at revealing smaller-scale features of brain structure than standard techniques. This project will test whether new rsi-based measures can resolve small-scale pathways thought to be affected by ad, accurately predict which individuals will decline cognitively, and correlate with other known markers of alzheimer's disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016241f name of organization or government: university of pennsylvania school of medicine. (h) purpose of grant: alzheimer's disease research by david irwin, md entitled: (a2016244s) genetic risk and clinical expression of tauopathy across alzheimer's disease and frontotemporal dementia. Investigator's summary: alzheimer's disease (ad) is defined by the presence of amyloid plaques and tau tangles in the brain associated with memory loss; however, a significant number of patients with ad have non-memory symptoms, such as language or visuospatial impairment. The underlying biology of these non-amnestic ad patients is understudied. Further understanding of the genetic influence and progression of tau pathology in non-amnestic ad will improve the diagnosis of patients who may benefit from emerging therapies that aim to halt or slow the progression of plaques and tangles in the brain and also identify new genetic targets for drug development in ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016244s name of organization or government: georgetown university. (h) purpose of grant: alzheimer's disease research by xiong jiang, phd entitled: (a2016251s) a novel multimodality mri biomarker of asymptomatic alzheimer's disease. Investigator's summary: alzheimer's disease (ad) is a neurodegenerative disease and the most common cause of dementia. With no known cures or disease-modifying therapies, there is a pressing need to find biomarkers that can accurately assess and predict disease progression in asymptomatic patients. However, despite recent efforts and significant progress in research, finding such a biomarker remains a major challenge. Given that ad is hypothesized to lead to changes in neuronal fu”

“Name of organization or government: the cleveland clinic foundation. (h) purpose of grant: alzheimer's disease research by dianne perez, phd entitled: (a2016272s) novel alpha1a-adrenergic receptor agonists to treat alzheimer's disease. Investigator's summary: we need to develop new drugs to treat alzheimer's disease (ad) that work in different ways than current treatments because current drugs and clinical trials are not promising or are not very effective. We have identified a novel target to treat ad and can show evidence that making drugs against this target will improve both the symptoms as well as repair or protect against the brain damage caused by this disease. This project is important in order to validate the target and then to actually make new drugs that are the most selective for this target, then test these drugs in an animal model of the disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016272s name of organization or government: the university of texas southwestern medical center. (h) purpose of grant: alzheimer's disease research by mark henkemeyer, phd entitled: (a2016345s) ephb receptors: novel pro-synaptic therapeutic targets for alzheimer's disease. Investigator's summary: alzheimer's disease (ad) slowly progresses as more and more synapses in the brain are destroyed. This first causes a gradual decline in memories and eventually inevitably leads to dementia and death. Ephb receptors are important proteins for synapse function and health, as they hold hands with the nmda receptor protein to help our brains store memories. Ephb also has the unfortunate ability to hold hands with plaque-forming amyloid-beta (a-beta) peptides made to ever increasing levels in alzheimer's disease, and this rise in a-beta targets ephb for degradation, resulting in a reduction in synapses and memories. Using novel high-throughput screens of small drug-like chemical libraries for compounds that disrupt the ability of ephb to bind with a-beta, i aim to discover a new class of medicines that will halt the destruction of synapses and avert memory loss with direct implication for the prevention of ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016345s name of organization or government: mayo clinic jacksonville. (h) purpose of grant: alzheimer's disease research by chia-chen liu, phd entitled: (a2016346f) effects of peripheral apoe isoforms on inflammation, brain vasculature, and alzheimer's disease pathogenesis. Investigator's summary: studies show that having apolipoprotein e4 (apoe4) gene mutation and blood vessel diseases (such as hypotension and diabetes) increase a person's risk for alzheimer's diseases (ad). Due to the blood-brain barrier (bbb), a protective layer that selectively prevents large molecules in the bloodstream from entering into the brain, the apoe produced in the liver and circulated in the bloodstream (periphery) does not mix with apoe produced in the brain. Using our unique mouse model in which apoe is produced only in the liver, our studies will for the first time test how peripheral apoe affects blood vessel health, brain functions, and ad disease progression. Our findings will be very useful in understanding how apoe4 impairs brain health and may ultimately lead to effective treatments for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016346f name of organization or government: j. David gladstone institutes. (h) purpose of grant: alzheimer's disease research by tara tracy, phd entitled: (a2016360f) deficient kibra signaling at synapses in alzheimer's disease. Investigator's summary: alzheimer's disease (ad) afflicts many elderly people in our society; however, there are few treatment options available and no known cure for this devastating disease. The structures by which neurons communicate with each other in the brain, called synapses, are especially vulnerable to toxicity in ad. My research”

“Name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by doo yeon kim, phd entitled: (a2016362s) altered neural function in a human 3d culture model of alzheimer's disease. Investigator's summary: in this proposal, we will further develop and characterize our human "alzheimer's disease in a dish" model based on the unique three-dimensional (3d) human neural progenitor cell culture technique. In our recent publication and preliminary studies, we have shown that human 3d cell culture model can recapitulate key events in alzheimer's disease (ad), which has not been feasible in ad models based on animals. Here, we will investigate mechanisms underlying these pathogenic events, including amyloid beta (a-beta), tau tangles, abnormal neuronal activity, synaptic/cellular injury and potentially neurodegeneration. If successful, our studies will provide a novel and valid platform for basic mechanistic studies and drug screening in a human brain-like environment, which could largely accelerate ad drug discovery. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016362s name of organization or government: tufts university. (h) purpose of grant: alzheimer's disease research by selene lomoio, phd entitled: (a2016379f) role of gga3 in bace1 axonal trafficking. Investigator's summary: neurons, highly organized brain cells, are characterized by specialized projections called dendrites and axons. The axon is the longest neuronal projection where proteins move like along a highway, in two different directions and at different speeds. Scientists have demonstrated that in the brain of persons affected by alzheimer's disease (ad), a disorder characterized by memory loss, this coordinated traffic pattern doesn't work properly, so neurons start to be unhealthy and die. Our goal is to try to understand why this traffic is no longer functioning in order to find a way to prevent the neuronal traffic disruption and possibly find a treatment for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016379f name of organization or government: university of texas southwestern medical center. (h) purpose of grant: alzheimer's disease research by joachim herz, md entitled: (a2016396s) targeting the endosome for alzheimer's drug discovery. Investigator's summary: apolipoprotein e4 (apoe4) status is the primary and biomedically most important risk factor for alzheimer's disease. We have found a novel mechanism by which apoe4 weakens synaptic strength in neurons, which led us to identify a promising novel drug target, nhe6. This proposal aims to establish the necessary mechanistic and infrastructural baseline to screen for nhe6 specific inhibitors and for discovering novel potential methods to target nhe6 function in vitro and in vivo. This is necessary for the evolution of a conceptually novel and therapeutically effective preventive approach to ad, at least for the majority of patients carrying the apoe4 allele. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016396s name of organization or government: university of tennessee health science center. (h) purpose of grant: alzheimer's disease research by catherine kaczorowski, phd entitled: (a2016397s) system genetics to identify modifiers of alzheimer's disease. Investigator's summary: the age of onset and severity of alzheimer's disease (ad) is subject to extreme variation across the human population. Despite millions of dollars and decades of research, over 70 percent of this variation remains unexplained. This proposal seeks to identify genes that modify the onset and severity of ad in a well-characterized, genetically diverse mouse population. Subsequent gene therapy will be used to validate identified genes and rescue/treat memory failure in a mouse model of ad. Results of this research will make a significant contribution to the understanding of the”

“Name of organization or government: weill cornell medical college. (h) purpose of grant: alzheimer's disease research by wenjie luo, phd entitled: (a2016399s) retromer chaperone r33 selectively promotes amyloid-beta degradation by microglia. Investigator's summary: accumulation of abnormal amyloid and tau proteins in the brains are believed to be detrimental for brain functions; thus searching for ways to reduce these bad proteins from the brain may help us find a promising drug for ad. We have found that a small chemical molecule can make microglia, a special brain cell with capability to clean up these bad proteins, and help them work more efficiently in clearance of amyloid proteins. This project will produce important information for us to understand how this small chemical helps microglia clean up amyloid proteins. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016399s name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by rachel bennett, phd entitled: (a2016404f) blood vessel changes in tauopathy. Investigator's summary: we have observed that tau, a key player in alzheimer's disease (ad), leads to blood vessel changes and increased expression of proteins involved in new blood vessel growth in the brains of mice. We do not know if these changes contribute to cell death and accumulation of ad proteins. This research aims to determine if blood vessel alterations are an early or late event in the disease process and to use "off the shelf" drugs to prevent blood vessel growth. Altogether, these studies will determine if the observed changes are harmful and may point towards widely available treatment options that should be considered for alzheimer's disease patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016404f name of organization or government: yale university. (h) purpose of grant: alzheimer's disease research by swetha gowrishankar, phd entitled: (a2016411f) elucidating the role of altered axonal lysosome transport in alzheimer's disease. Investigator's summary: a robust feature of alzheimer's disease (ad) brain pathology is the accumulation of lysosomes (digestive organelles of cells) in swollen neuronal axons that surround amyloid plaques. How these lysosomes come to accumulate and what their role is in ad has not been established. While a major function of lysosomes is to degrade proteins, our recent work investigating these plaque-associated lysosomes demonstrated that they lack the enzymes required for efficient protein degradation. This suggests a model wherein amyloid plaques cause a blockade in the transport and maturation of lysosomes in surrounding neuronal axons. These immature lysosomes appear to contain the machinery required to make more of the amyloid beta peptide that is the major component of amyloid plaques. Thus, the interactions between amyloid plaques and neuronal axons are predicted to result in a vicious cycle that contributes to further disease pathology. My proposed research aims to test this hypothesis comprehensively by establishing a neuronal primary culture model for such axonal lysosome transport defects. This system will be amenable to drug manipulations and genetic perturbations to elucidate both the mechanisms that control lysosome biogenesis and transport in neuronal axons, as well as the impact of impaired lysosome transport on the amyloidogenic processing of the amyloid precursor protein (app). I will furthermore investigate the effects of lysosome axonal transport defects on ad brain pathology (such as amyloid plaque growth and number) through the use of genetic perturbations in a mouse model of ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016411f name of organization or government: brigham and women's hospital. (h) purpose of grant: alzheimer's disease research by qiaoqiao shi, phd entitled: (a2016425f)”

“Name of organization or government: university of pennsylvania. (h) purpose of grant: alzheimer's disease research by laura wisse, phd entitled: (a2016432f) the medial temporal lobe in preclinical alzheimer's disease and aging. Investigator's summary: drug trials are increasingly being started in an early stage of alzheimer's disease (ad) before memory problems start, to prevent brain damage from becoming too severe. To test how well such a treatment is working, we need a good measure that can track the treatment effects in the brain. A good candidate for that is the brain region known as the medial temporal lobe, because it is affected in an early stage of ad. However, a fact that complicates using the medial temporal lobe as a marker is that this brain region is also affected in normal aging. To separate the effects of preclinical ad from normal aging, we plan to investigate the medial temporal lobe with a more precise, high resolution magnetic resonance imaging scanner, which will allow us to investigate smaller regions within this brain region which, in contrast to the cruder measurements, are expected to show differential effects of aging and preclinical ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016432f name of organization or government: mclean hospital. (h) purpose of grant: alzheimer's disease research by jennifer gatchel, md, phd entitled: (a2016434f) depressive symptoms and tau pet imaging in early alzheimer's disease. Investigator's summary: in alzheimer's disease (ad), changes occur not only in a person's memory and thinking, but also in their mood and behavior; symptoms such as depression, apathy and withdrawal are common and distressing to patients and their families, and can be just as debilitating, if not more so, than changes in memory and thinking. These psychiatric and behavioral symptoms may occur very early in the disease process, in the "pre-alzheimer's" disease stage, when a person may have the ad proteins, amyloid beta (a-beta) and tau, in their brains, but before they have developed overt signs of the disease. There is currently not a clear understanding of why and how these debilitating psychiatric and behavioral symptoms occur, and there are few effective treatments. Visualizing a-beta in the brains of older adults, and now, due to an exciting new technology developed in our group that will also allow us for the first time to visualize the tau protein in the brains of living older adults, this project will be vital by 1) allowing us to see how mild psychiatric and behavioral symptoms relate to build up of a-beta, tau, and brain pathway changes in normal older adults and those in the pre-alzheimer's and early ad stages, and 2) providing important information about patterns of psychiatric and behavioral symptoms that may help us to identify those most at risk, all of which will pave the way for developing more effective treatments and prevention strategies for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016434f name of organization or government: university of texas at austin. (h) purpose of grant: alzheimer's disease research by stephen martin, phd entitled: (a2016443s) a new approach to treating alzheimer's disease. Investigator's summary: alzheimer's disease (ad) is the most prevalent, neurodegenerative disease affecting the elderly, but all approved medications for ad only temporarily address the symptoms, not the progression, of ad. Because there is an urgent, unmet need for drugs to treat both the symptoms and the disease, the proposed program will explore a novel strategy to treat ad by targeting a biological pathway different from those of all existing drugs and known clinical candidates. If successful, a compound will be identified that holds promise for those suffering from ad, thus representing a new way to treat this devastating disease. For more information, visit the brightfocus website: www.brightfocus.or”

“Name of organization or government: icahn school of medicine at mount sinai. (h) purpose of grant: alzheimer's disease research by jean-vianney haure-mirande, phd entitled: (a2016482f) role of tyrobp in the pathogenesis of alzheimer's disease. Investigator's summary: recent studies highlight the possible role of the immune system in alzheimer's disease (ad). The immune system and its activation can be a "double-edge sword" event in ad: on one hand, it can protect the brain by reducing the formation of amyloid plaque but on the other hand, it can induce brain inflammation and have deleterious effects. The aim of our project is to: 1) understand the role of the immune system in the pathogenesis of ad, and 2) provide new insight for a therapeutic target to control ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016482f name of organization or government: emory university. (h) purpose of grant: alzheimer's disease research by zixu mao, phd entitled: (a2016501s) autophagy in microglial activation and neuroinflammation. Investigator's summary: scientists now believe that chronic inflammation of the brain is an important cause of alzheimer's disease and treating inflammation can reduce one's chance of getting the disease. Scientists know which types of brain cells are most important for causing the brain inflammation but do not have a good understanding of why and how this occurs. The proposed study will help us answer these important questions. It may allow us to find new ways to treat brain inflammation to slow or prevent the disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016501s name of organization or government: icahn school of medicine at mount sinai. (h) purpose of grant: alzheimer's disease research by stephen salton, md, phd entitled: (a2016508s) role of vgf in alzheimer's disease pathogenesis and progression. Investigator's summary: previous work from our lab and others has demonstrated a significant decline in the expression of the neuronal protein vgf, which is a nerve growth factor, in the brains of patients with alzheimer's disease (ad) and amyotrophic lateral sclerosis. Moreover, a number of biomarker studies have identified that vgf-derived peptides in the cerebrospinal fluid (csf) are decreased in patients with ad but not in control patients. These data indicate that decreased vgf expression in the brain and csf is associated with neurodegenerative disease; we propose to investigate whether this decline is mechanistically involved in the pathogenesis or progression of ad. In preclinical studies, we will investigate the potential mechanisms by which vgf delays or reverses memory dysfunction and neuropathology in a mouse model of ad, and lastly will investigate whether a vgf-derived peptide could be therapeutically harnessed to suppress memory impairment in these mice, providing a strong foundation for future exploration of approaches that deliver vgf and/or vgf-derived peptides to patients with ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016508s name of organization or government: boston university. (h) purpose of grant: alzheimer's disease research by tsuneya ikezu, md, phd entitled: (a2016551s) novel trem2 reporter platform for drug discovery. Investigator's summary: we propose to identify a drug, which can enhance clearance of an unwanted buildup of protein fibril and dead cells in the alzheimer's disease (ad) brain. For that purpose, we will focus on a new molecule, triggering receptor expressed on myeloid cells 2 (trem2), which has never been tested for the development of a drug. The molecule is expressed on the surface of immune cells and facilitates their uptake of protein fibrils or dead cells. We will validate the candidate drugs on tissue-cultured cells from humans, and on animal models of ad. Our long-term goal is to discover a prophylactic and therapeutic drugs for the treatment of ad. F”

“Name of organization or government: university of california, los angeles. (h) purpose of grant: alzheimer's disease research by paul seidler, phd entitled: (a2016588f) tau structures: from proteopathic to protective. Investigator's summary: the work outlined in this proposal will expand our understanding of alzheimer's disease by delineating the structural assemblies that are available to tau. Toxic forms of the protein will be determined and used to template the design of peptide agents that block the assembly of these structures. Natural variations in tau that protect against the formation of toxic assemblies will be studied to uncover new possibilities for therapeutic intervention, and to gain insights into the mechanisms by which amyloid fibers form, propagate, and exert toxicity. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2016588f name of organization or government: johns hopkins bayview medical center. (h) purpose of grant: alzheimer's disease research by constantine lyketsos, md, mhs entitled: (c2015500) accelerating the development, testing and dissemination of home base demensia care intervention. 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.”

“Name of organization or government: augusta university research institute. (h) purpose of grant: national glaucoma research by yutao liu, phd entitled: (g2016023) mir-182 and trabecular meshwork dysfunction in high tension glaucoma. Investigator's summary: primary open-angle glaucoma (poag) is the most common type of glaucoma and lowering eye pressure is the main approach to treating poag in the clinic. The purpose of this proposal is to study how a short rna molecule mir-182 may affect the outflow of the clear liquid in the front part of human eyes. We will examine how this short rna affects eye pressure using an integrative approach. This study may generate therapeutic targets to control eye pressure in human glaucoma patients with high eye pressure. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016023 name of organization or government: research foundation for the state university of new york. (h) purpose of grant: national glaucoma research by xiuqian mu, md, phd entitled: (g2016024) generation of retinal ganglion cells by reprograming. Investigator's summary: glaucoma is a disease that causes vision loss and blindness in millions of people. This proposal aims at improving existing and establishing new procedures to generate retinal ganglion cells, the cells affected in glaucoma, in a petri dish. The cells thus produced will be used to study the reasons causing glaucoma, to screen for drugs to treat it, and to develop new therapeutic strategies. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016024 name of organization or government: georgia institute of technology. (h) purpose of grant: national glaucoma research by raquel lieberman, phd entitled: (g2016027) identification of myocilin posttranslational modifications and binding partners under static and glaucoma-relevant mechanical stretch. Investigator's summary: myocilin, a protein molecule associated with two specific forms of glaucoma, is expressed at high levels in the eye tissue whose malfunction is linked to the most common risk factor for glaucoma, ocular hypertension. To this day, the normal function of myocilin in the eye tissue, and elsewhere in the body, remains unknown. Here we will use knowledge of the myocilin structure and modern proteomics techniques to identify changes in myocilin and interacting partners under distinct glaucoma-relevant environments. This research will help clarify myocilin function and will lead to new targets for novel anti-glaucoma therapies. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016027 name of organization or government: university of pittsburgh. (h) purpose of grant: national glaucoma research by kevin chan, phd entitled: (g2016030) widespread structural and functional brain changes and visuomotor impairments in glaucoma. Investigator's summary: glaucoma is the second leading cause of blindness worldwide, and falls are a major health concern in glaucoma patients. Recently, increasing evidence suggests that glaucoma is not an eye-only disease but also involves widespread changes in the brain, but its causes and the potential clinical and behavioral effects on visuomotor function remain unclear. The goal of the proposed project is to understand how glaucoma may impair the brain structurally and functionally within and beyond the visual pathway, and whether the brain changes in glaucoma are associated with early vision loss or balance and mobility impairments. The findings will improve our understanding of the mechanisms of visuomotor impairments in glaucoma and ultimately guide vision preservation and falls-related interventions to individual patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016030”

“Name of organization or government: the schepens eye research institute. (h) purpose of grant: national glaucoma research by meredith gregory-ksander, phd entitled: (g2016081) the nlrp3 inflammasome as a new target in glaucoma. Investigator's summary: it is believed that glaucoma develops when a part of the eye containing nerves (the optic nerve head) is stressed and damaged. Inflammation is part of the body's wound healing response to injury, but if this response becomes chronic it can lead to scarring and loss of function. Our project identifies an important new regulator of inflammation in the optic nerve head and tests whether inhibiting this regulator will stop disease development and vision loss. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016081 name of organization or government: university of california, san francisco. (h) purpose of grant: national glaucoma research by yvonne ou, md entitled: (g2016084) retinal synapse disassembly in glaucoma. Investigator's summary: in glaucoma, the cells of the optic nerve die and that can lead to blindness. Although we know that optic nerve cells are injured in glaucoma, we do not yet understand the steps between optic nerve cell injury and death. A detailed understanding of the earliest changes that occur will allow us to design treatments that can rescue these injured optic nerve cells before irreversible cell death occurs. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016084 name of organization or government: boston university school of medicine. (h) purpose of grant: national glaucoma research by haiyan gong, md, phd entitled: (g2016099) cell-cell interaction in giant vacuole/pore formation. Investigator's summary: normal pressure inside of the eye is maintained through a dynamic balance between aqueous humor production and drainage, and higher eye pressure is commonly associated with primary open-angle glaucoma (poag), a disease that is a leading cause of blindness worldwide. For aqueous humor to drain out of the eye, it needs to exit through a tube, schlemm's canal (sc), and two unique structures can be found in the cells that line the wall of sc: giant vacuoles, which are pressure-dependent outpouchings, and pores, which are openings. Previous studies have shown that a reduction in the density of both giant vacuoles and pores occurs in the eyes with poag, indicating that this reduction can potentially contribute to the elevated outflow resistance characteristic of this disease. We propose to study two types of cellular interactions in the cells that line sc using a newly developed, advanced 3d electron microscopy technology. The major goal of this project is to determine whether each of these two types of cellular interactions plays a role in regulating aqueous outflow by influencing giant vacuole and pore formation. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016099 name of organization or government: board of regents, university of wisconsin system. (h) purpose of grant: national glaucoma research by gillian mclellan, bvms, phd entitled: (g2016129) tgf-beta and glaucoma progression in a spontaneous model. Investigator's summary: glaucoma remains a leading cause of vision loss globally, and it is estimated that over 76 million people will be affected this disease by 2020. There is mounting evidence that a chemical growth factor, transforming growth factor beta (tgf-beta), plays an important role in processes that lead to damage to the optic nerve, resulting in vision loss. This research seeks to understand how we might protect the optic nerve from damaging effects of tgf-beta and will test a promising new treatment strategy for glaucoma patients by repurposing an existing drug to block tgf-beta and preserve vision. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016129”

“Name of organization or government: massachusetts eye and ear infirmary. (h) purpose of grant: national glaucoma research by daniel sun, phd entitled: (g2016137) do we need optic nerve head astrocytes to become reactive in glaucoma? Investigator's summary: we still don't know how people lose their vision in glaucoma. To date, we have a strong idea of where in the eye the damage begins, but the biological processes happening at this location, and the cells that are involved, remain unclear. This is important to find out if we want to be able to better target therapeutic interventions. My research focuses on better understanding the role that a type of supporting cell called astrocytes plays in the biological process of glaucoma, ie, whether they help to slow down the vision loss in glaucoma or make it worse. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016137 name of organization or government: mount sinai school of medicine. (h) purpose of grant: national glaucoma research by audrey bernstein, phd entitled: (g2016151) autophagic dysfunction in exfoliation glaucoma. Investigator's summary: in exfoliation syndrome (xfs), the eye starts accumulating "white fluff" deposits composed of protein aggregates. The aggregates eventually block the exit of fluid from the eye, causing a buildup of pressure that can lead to blindness. We have discovered that cells obtained from xfs eyes may have a problem degrading these protein aggregates, leading to an accumulation of "cellular trash" that becomes toxic. In this proposal, we will test methods to accelerate degradation of this cellular waste to improve the health of xfs cells. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016151 name of organization or government: medical university of south carolina. (h) purpose of grant: national glaucoma research by shahid husain, phd entitled: (g2016157) pro-inflammatory cytokines regulation by hif-1 alpha in glaucoma. Investigator's summary: in glaucoma, neurons are dying slowly and leading to blindness. Numerous detrimental factors, including low oxygen (hypoxia), play key roles in the progression of this disease. Our team has shown that the neurotoxic proteins, including cytokines and hypoxia-inducible transcription factor-1 alpha (hif-1 alpha) are up-regulated and facilitate neuronal death in glaucoma. The proposed studies in this project will limit the up-regulation of such neurotoxic proteins to slow/halt the neuronal death in glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016157 name of organization or government: university of alabama at birmingham. (h) purpose of grant: national glaucoma research by crawford downs, phd entitled: (g2016165) continuous telemetric measurement and chronic control of cerebrospinal fluid pressure.investigator's summary: the pressure inside the eye has long been thought to play a dominant role in glaucoma, a blinding disease, but recent work suggests that the fluid pressure surrounding the nerve exiting the eye is also involved. These pressures are not easy to measure, so there has been no good way to determine if the pressure around the nerve is truly important in glaucoma. We have developed a new system to wirelessly measure and record the pressure in the eye continuously in research subjects, and we now want to extend that system to measure the pressure around the nerve exiting the eye. Using this system, we can definitively determine if the pressure around the nerve is important in glaucoma, which could lead to new treatment approaches for this blinding disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2016165”

“Name of organization or government: the schepens eye research institute. (h) purpose of grant: macular degeneration research by petr baranov, md, phd entitled: (m2016046) indirect photoreceptor neuroprotection through small molecule-induced growth factors. Investigator's summary: we aim to identify small molecules that can induce endogenous growth factors in the sensory part of the eye the retina. Our overall goal is to investigate the power of this indirect neuroprotection approach to rescue photoreceptors and ganglion cells from death, overcoming limitations usually associated with growth factor delivery. The results of our studies should lead to the development of novel, accessible and effective molecular therapies for retinal dystrophies and other neurodegenerative disorders. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016046 name of organization or government: west virginia university. (h) purpose of grant: macular degeneration research by jianhai du, phd entitled: (m2016047) nad metabolism in normal and disease-specific human retinal pigment epithelial cells. Investigator's summary: some eye diseases, like age-related macular degeneration, cause blindness because the light-sensing cells and their support cells in the eye stop working. We believe that one of the reasons the support cells stop working is because their ability to generate energy for themselves is damaged. We would like to understand how this damage occurs and to test whether new nutritional supplements, called nicotinamide adenine dinucleotide (nad) metabolites, can improve their ability to continue to survive and function. If these new supplements can rescue the support cells when studied in a cell culture dish and in a mouse model, we believe they may be able to slow or stop vision loss in patients with amd and other similar retinal diseases. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016047 name of organization or government: johns hopkins university. (h) purpose of grant: macular degeneration research by debasish sinha, phd entitled: (m2016056) modulating lysosomal function in retinal pigment epithelial as a novel therapeutic approach for the treatment of amd. Investigator's summary: age-related macular degeneration is the leading cause of blindness among the elderly and currently there is no known treatment for early age-related macular degeneration (amd). Therefore, we want to focus our studies at this early phase in order to develop prevention and treatment before this disease advances and causes dramatic vision loss. Our proposed studies are aimed at developing novel small molecules that could be tested as a therapy for early amd. Such studies have great clinical significance since they can provide a novel therapeutic approach for the management of amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016056 name of organization or government: university of pittsburgh. (h) purpose of grant: macular degeneration research by jeffrey gross, phd entitled: (m2016067) a zebrafish model of amd: a novel approach to identify factors that facilitate rpe regeneration and functional restoration. Investigator's summary: geographic age-related macular degeneration (amd) results from the progressive death of the retinal pigment epithelium (rpe), triggering photoreceptor degeneration in the retina and ultimately, in blindness; we have no effective therapies to slow the degeneration or restore lost rpe cells. In contrast to mammals, zebrafish possess a remarkable ability to regenerate lost tissues after injury, and they are a heavily utilized model system for studying the process of retinal regeneration. Our research demonstrates, for the first time, that they can also repair damage to the rpe and experiments planned in this proposal seek to understand this process by identifying critical factors required to initiate and sustain the regenerative response. Once”

“Name of organization or government: university of tennessee health science center. (h) purpose of grant: macular degeneration research by francesco giorgianni, phd entitled: (m2016068) in vitro and in vivo studies of cd5l/aim as a possible key role player in drusen biogenesis. Investigator's summary: we have discovered that certain cells of the eye, termed retinal pigment epithelium (rpe), that are typically damaged in a common disease of the elderly called age-related macular degeneration (amd), express a protein that is targeted by the immune system of patients who have amd by means of auto-antibodies. This protein we discovered in the rpe is cd5l/aim, which is a secreted scavenger receptor protein, and we have evidence suggesting that cd5l/aim is very important in helping the rpe clear damaged lipoproteins (called oxldl) that, in amd, accumulate under the rpe to form drusen, a deposit that is the first and most typical evidence that an eye has developed amd. Thus, we will culture rpe cells in vitro to prove that cd5l/aim is a key molecule in clearing oxldl and that, when blocked by an antibody just like what we see happens with auto-antibodies in patients who have amd, the rpe cells will no longer be able to clear oxldl. Lastly, to understand how the presence of auto-antibodies in the bloodstream of patients with amd relates to disease in affected patients, we will study serum samples from amd patients and correlate the levels of anti-cd5l/aim auto-antibodies with how many drusen they have at the back of their eyes, as well as with certain genetic factors that are known to increase the risk of developing amd. This will allow us to test the hypotheses that the more auto-antibodies one has against cd5l/aim, the more drusen we are likely to find at the back of the eye, which would suggest that certain auto-antibodies facilitate formation of drusen in patients who have amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016068 name of organization or government: the cleveland clinic foundation. (h) purpose of grant: macular degeneration research by vera bonilha, phd entitled: (m2016079) geographic atrophy: changes in the retinal pigment epithelial and inflammatory cell populations in the region of expanding lesions. Investigator's summary: age-related macular degeneration (amd) is a complex disease leading to irreversible blindness of the elderly population in industrialized countries. At the moment, a few effective treatments exist for this disease, but new treatments effective to the different symptoms of the disease are urgently needed. This research project will correlate imaging of the atrophic late-stage lesion of amd donor eyes with findings with detailed morphological and cellular analysis in and around the leading edge of these lesions. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016079 name of organization or government: doheny eye institute. (h) purpose of grant: macular degeneration research by zhihong hu, phd entitled: (m2016088) automated multimodal detection and analysis of geographic atrophy. Investigator's summary: geographic atrophy (ga) is a form of age-related macular degeneration (amd), and increasingly the main cause of vision loss in patients. Much of the previous research of ga has focused on individual imaging modalities, utilizing two-dimensional (2d) information alone. However, considering the 3d topology of the disease, utilizing information from all imaging modalities concomitantly could potentially yield a more precise and comprehensive depiction of ga lesions. The overall goal of this project is to develop an automated multimodal ga segmentation system to more precisely quantify ga progression over time in multimodal 2d and 3d images to facilitate the understanding of ga's relationship to vision loss. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016088 name of organization or government: john”

“Name of organization or government: joan and sanford i. Weill med. Coll. Of cornell univ.. (h) purpose of grant: macular degeneration research by marcelo nociari, phd entitled: (m2016124) lipofuscin-mediated endoplasmic reticulum stress in the pathogenesis of macular degeneration. Investigator's summary: as retinal pigment epithelium (rpe) gets old, it accumulates a lot of lipid bisretinoids (lbs). Above a certain threshold, or after exposure to light, lbs become toxic and may induce cell death. Many groups have previously identified mechanisms by which lbs damage the rpe. These studies, however, did not provide us with a method to clear lbs or alleviate their harmful effects. Working with cultures of rpe cells and synthetic lbs, we found a novel mechanism by which lbs kill rpe cells. This mechanism seems to be central to lb toxicity and is amenable to inhibition with drugs, as we have already identified two chemical compounds that fully prevent rpe cell death by lbs. Interestingly, some of these drugs are being tested for the treatment of neurodegeneration in parkinson's and alzheimer's disease. In the current project, we propose to characterize well this new damaging mechanism, prove that it contributes significantly to lb-induced retinal degeneration in the eye, and test if drugs that block this mechanism can prevent blindness in an animal model of amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016124 name of organization or government: university of california, riverside. (h) purpose of grant: macular degeneration research by kaustabh ghosh, phd entitled: (m2016161) micromechanical determinants of choriocapillaris dysfunction in amd pathogenesis. Investigator's summary: aging is an important risk factor for age-related macular degeneration (amd). Aging is also associated with an increase in tissue stiffness. Yet, whether and how progressive tissue stiffening contributes to the worsening of this debilitating and degenerative eye disease remains unknown. The aim of this proposal is to address this gap in knowledge by using an innovative and interdisciplinary approach, so that new and potentially superior treatments can be developed to treat this condition in the future. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016161 name of organization or government: massachusetts eye and ear infirmary. (h) purpose of grant: macular degeneration research by kip connor, phd entitled: (m2016183) lipid regulators of choroidal neovascularization. Investigator's summary: in wet or neovascular age-related macular degeneration (amd), abnormal blood vessels grow from beneath the retina that are immature in nature and leak fluid below or within the retina, leading to a rapid loss in eyesight. Emerging data implicate lipids derived from the cytochrome p450 pathway act as potent regulators of angiogenesis. Thus, it is of great clinical interest to elucidate the mechanisms by which these lipid mediators facilitate disease development and/or regression. Our proposal has clear potential to lead to new therapeutic molecules, targets, and strategies for specifically inhibiting neovascular amd, a leading cause of blindness in the elderly which, if left untreated, rapidly leads to substantial vision loss. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016183 name of organization or government: usc eye institute. (h) purpose of grant: macular degeneration research by biju thomas, phd entitled: (m2016186) studies on functionality of ips-rpe transplanted in immunodeficient rcs rats. Investigator's summary: dysfunction and death of retinal pigment dpithelium (rpe) has been observed in various human retinal degenerative diseases that lead to blindness, such as amd. We propose to treat such diseases by transplanting a polarized monolayer of rpe sheets derived from human induced pluripotent stem cells (ips). To minimize the immunological reactions, a ne”

“Name of organization or government: johns hopkins university. (h) purpose of grant: macular degeneration research by malia edwards, phd entitled: (m2016198) retinal glial changes in amd. Investigator's summary: age-related macular degeneration (amd), the leading cause of blindness in people over 60 years of age, is a complex disease that involves many cells. Two cells that have been largely ignored with regards to amd are astrocytes and m ller cells. Since these cells maintain a stable retinal environment and communicate with many cells, disruption to their normal behavior could contribute to the amd disease process. The proposed research will investigate why astrocytes exit the retina in amd, potentially identifying novel therapeutic targets. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016198 name of organization or government: university of texas sw medical center. (h) purpose of grant: macular degeneration research by john hulleman, phd entitled: (m2016200) manipulation of a single gene for the treatment of malattia leventinese and dry age-related macular degeneration. Investigator's summary: malattia leventinese (ml) and age-related macular degeneration (amd) are two eye diseases that disrupt the normal physiology of the retina, the back portion of the eye which is responsible for sensing light. If these diseases are left unchecked, they can interfere with a person's vision, and in some cases, result in blindness. The overall goal of this project is to reduce the levels of a single protein which is involved in the pathogenesis of both ml and amd. By reducing the levels of this protein, we anticipate that we will significantly slow or halt disease progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016200 name of organization or government: university of california, santa barbara. (h) purpose of grant: macular degeneration research by patrick daugherty, phd entitled: (m2016219) antibody specificity repertoire characterization in amd. Investigator's summary: the immune system is involved in the development of age-related macular degeneration (amd). The objective of this project is to identify molecular targets of the immune response in amd. The large set of antibodies circulating in blood will be comprehensively analyzed to identify antibodies that occur in amd, and that will allow us to identify organisms from the environment that produce antibodies present in individuals with amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2016219 name of organization or government: scheie eye institute university of pennsylvania. (h) purpose of grant: macular degeneration research by benjamin kim, md entitled: (cm2016971) therapeutic evaluation of alpha lipoic acid for geographic atrophy. Name of organization or government: duke university eye center. (h) purpose of grant: macular degeneration research by mikael klingeborn, phd entitled: (m2015221) the role of exosomes in dry amd.”