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2021 Research Grants

Glaucoma Research Foundation (GRF) provides seed money for creative pilot research projects that hold promise.

To date, we have awarded more than 250 grants to explore new ideas in glaucoma research. Known as “Shaffer Grants for Innovative Glaucoma Research” in honor of GRF founder Dr. Robert N. Shaffer, the Shaffer Grants continue our longstanding commitment to one-year incubation grants to explore novel and promising ideas in the study of glaucoma.

The National Institutes of Health and large companies may pass over the young researcher with an innovative idea, if there is no precedent. Armed with evidence made possible by our research grants, scientists can often secure the major funding necessary to bring their ideas to fruition.

We consider it vital to invest funds in new high-impact research that may lead to major government and philanthropic support. All Glaucoma Research Foundation grants to explore new ideas are in the amount of $50,000.

The 2021 Shaffer Grants for Innovative Glaucoma Research are made possible through generous philanthropic support including leadership gifts from the Frank Stein and Paul S. May Grants for Innovative Glaucoma Research, the Harvey DuBiner MD Memorial Fund, Bob and Birdie Feldman and Giving Tuesday contributions, Molly and David Pyott, Richard and Carolyn Sloane, the Dr. Henry A. Sutro Family Grant for Research, Dr. James and Elizabeth Wise, and The Dr. Miriam Yelsky Memorial Research Grant.

Following is a summary of projects Glaucoma Research Foundation is currently funding.


The 2021 Shaffer Grants for Innovative Glaucoma Research


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Ta Chen Chang, MD

Bascom Palmer Eye Institute
Funded by the Harvey DuBiner, MD Memorial Fund

Project: Genetic Studies of Open Angle Glaucoma in Haitian Community

Summary: The objectives of this proposal are to identify the genes associated with primary open angle glaucoma (POAG) affecting the Haitian community by screening high-risk individuals for POAG. Glaucoma is the leading cause of irreversible blindness worldwide, with early detection/management being the best way to preventing blindness. POAG disproportionally affects Haitians individuals, with an earlier age of diagnosis and more severe disease on presentation compare to individuals of other races. The reason behind this disparity is unknown. POAG is highly heritable with several known genes, none of which has been well studied in the Haitian population. We hypothesize that the increased risk and aggressive course of POAG in Haitians may be due to one or several POAG genes being overrepresented in the population due to Haiti’s relative geographic and cultural isolation. Collectively, the work proposed is expected to establish the first high quality glaucoma genetic database of the Haitian population. This rich database will increase the diversity of glaucoma genetic study populations and lay the key steps to the personalized approach of glaucoma care (including gene-based screening strategies and therapeutics) for the Haitian community.

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Qi N. Cui, MD, PhD

Stellar-Chance Laboratories, University of Pennsylvania
Funded by Dr. James and Elizabeth Wise

Project: Evaluating the Glucagon-like Peptide 1 Receptor (GLP-1R) as a Therapeutic Target in Glaucoma

Summary: Glaucoma is characterized by death of retinal ganglion cells. For patients with glaucoma, intraocular pressure reduction is the only therapeutic mechanism available to slow disease progression. Unfortunately, successful pressure lowering does not prevent disease progression in a significant number of patients. Recent studies have implicated neuroinflammation in the pathogenesis of glaucoma. Evidence from our lab and others suggest that pro-inflammatory microglia and macrophages respond to ocular hypertension by inducing astrogliosis to cause retinal ganglion cell loss. Furthermore, once present, retinal inflammation persists beyond intraocular pressure normalization. NLY01, an agonist for the glucagon-like peptide 1 receptor (GLP-1R), effectively prevents astrogliosis in ocular hypertension to rescue retinal ganglion cells. GLP-1R class of therapeutic agonists is efficacious and safe in the long-term treatment of type 2 diabetes. We hypothesize a multi-hit hypothesis of glaucoma pathogenesis, whereby RGC-autonomous mechanism of pressure-induced cell stress acts in concert with non-cell autonomous mechanism of retinal inflammation to trigger neuronal cell death. We will test this hypothesis using three models of glaucoma. In parallel, we will examine whether NLY01, and more broadly GLP-1R agonists, may be a viable therapeutic adjunct to existing pressure modifying therapies for glaucoma.

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Luca Della Santina, PhD, PharmD

University of California, San Francisco
Funded by the Frank Stein and Paul S. May Grants for Innovative Glaucoma Research

Project: Excitatory - Inhibitory Balance in Glaucoma

Summary: Diagnosis of glaucoma often occurs when a significant amount of retinal ganglion cells die and vision is lost. Some early sub-clinical alterations occurring in this disease involve loss of synapses inside the retina. Synapses can either excite or depress the retinal ganglion cells and balance between these two types of synapses constitute a key factor regulating the function of ganglion cells. We have demonstrated that excitatory synapses are lost but we still don’t know how the balance between excitatory and inhibitory synapses is modified in glaucoma. Our project proposes to study both kinds of synapses in a model of glaucoma, where we can control the time at which ocular pressure is increased. We will use our novel computer program ObjectFinder to analyze millions of synapses, using deep learning technology to recognize them, and monitor their integrity over time. With this innovative approach, we aim to discover which synapses are affected first when ocular pressure increases, and where in the retina they are located, allowing researcher to design more sensitive early screening tests for glaucoma that may help physicians to diagnose this disease before significant vision is lost.

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Jiun Do, MD, PhD

Shiley Eye Institute, University of California, San Diego
Funded by Richard and Carolyn Sloane

Project: Optic Nerve Relays for the Restoration of Visual Function

Summary: Optic neuropathies like glaucoma cause vision loss by irreversibly damaging the optic nerve and disrupting the connections between the eye and the brain. There are currently no therapies to repair this connection and restore vision. Therefore, there is a need for novel therapies to regenerate the optic nerve if restoring vision is to be possible. Stem cells have the potential to repair damage in the nervous system. Preliminary work has shown that stem cells placed in the injured optic nerve similarly survive and integrate with the visual system. In this proposal, I will explore how combining stem cells with gene editing can reform damaged circuits in the visual system and the degree to which stem cells connect to the brain. To people with glaucoma, this project is significant because it has the potential to regenerate the connections between the eye and the brain that are permanently lost due to glaucoma. The ability to reform these connections is necessary to restore vision. Therefore, this project could provide people with glaucoma who have lost vision with a treatment to restore vision.

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John Fingert, MD, PhD, FARVO

Carver College of Medicine, University of Iowa
Funded by the Dr. Henry A. Sutro Family Grant for Research

Project: Single Cell Transcriptome Analysis of Glaucoma

Summary: Glaucoma is one of the three most heritable human diseases, indicating that genes are very important in its pathogenesis. We previously discovered that mutations in two genes, myocilin (MYOC) or TANK binding kinase 1 (TBK1), cause human glaucoma and we engineered models with analogous mutations in these genes and showed they also develop glaucoma. Mutations in the TBK1 gene are one of the most common, known-molecular causes of human glaucoma, however, the mechanism by which a mutation in this gene causes nerve damage and blindness is not yet known. One way to investigate the biological processes that lead to glaucoma is to examine which genes are activated as the disease develops and progresses. In this application we propose to identify the pattern of gene activation that occurs eyes that develop glaucoma due to a TBK1 gene mutation. We will use a powerful new method, single cell RNA sequencing, to analyze retinal tissue. Our experiments will show which genes are activated in key cells/tissues of the eye at various times during the development of glaucoma. This data will provide a description of what goes wrong in the eyes of patients that have glaucoma at the finest molecular level. We will use these data as roadmap to describe the checkpoints of glaucoma development and to identify opportunities to prevent or halt progression of the damage to the eye that causes vision loss in glaucoma.

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Jason Meyer, PhD

Indiana University School of Medicine
Funded by Bob and Birdie Feldman and Giving Tuesday contributions

Project: Complement Pathway-mediated Neurotoxicity of Reactive Astrocytes in a Stem Cell Model of Glaucoma

Summary: Glaucoma is a common cause of vision loss characterized by the progressive degeneration of retinal ganglion cells (RGCs), the projection neurons of the retina that convey visual information to the brain. Astrocytes are closely associated with RGCs in the nerve fiber layer of the retina and optic nerve, where they play a vital role in supporting RGC homeostasis and function. However, during the course of disease, astrocytes acquire a “reactive” state that is known to contribute to neurodegeneration. However, neither the factors responsible for nor the specific mechanisms underlying reactive astrocyte-induced neurodegeneration have been completely identified, resulting in changes to how reactive astrocytes interact with RGCs. The complement cascade has been implicated in physiological processes during brain development and homeostasis, mainly involved in the maturation of synaptic circuits. Nevertheless, in disease conditions, the rapid and uncontrolled activation of the complement pathway leads to inflammation and neurodegeneration. The activation of the complement pathway has emerged as a potent modulator of reactive gliosis and neuronal damage, with the classical complement pathway involved in neuroinflammation, yet the exact mechanisms by which complement exacerbates neurodegeneration remain unclear. Recent studies have demonstrated that reactive astrocytes lead to RGC neurodegeneration in a model of glaucoma, and the characterization of astrocyte reactivity has revealed elevated complement C3 expression in astrocytes, characteristic of classical complement pathway activation. However, as many phenotypic and functional differences exist in both astrocytes and RGCs between models and humans, it is unclear how reactive astrocyte-specific changes exert their effects in the human retina. Hence, it is hypothesized that A1 reactive astrocytes mediate RGC neurodegeneration through the activation of the C3 complement pathway. In order to test this hypothesis, human pluripotent stem cell (hPSC)-derived astrocytes and RGCs will be utilized to study mechanisms underlying the toxic effects of reactive astrocytes upon RGCs in a human cellular model of glaucoma, with a subsequent analysis of how complement pathway activation leads to neurodegeneration.

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Lev Prasov, MD, PhD

Kellogg Eye Institute, University of Michigan
Funded by the Frank Stein and Paul S. May Grants for Innovative Glaucoma Research

Project: Elucidating the Role of a Novel Closure Associated Gene in Eye Development and Disease

Summary: Angle closure glaucoma is a blinding condition that affects 0.5% of the world’s population. It is caused by blockage of the drainage pathways in the eye, leading to acute or chronic elevations in eye pressure and subsequent damage to the optic nerve. This can lead to swift loss of vision. Disorders affecting the development or growth of the eye can lead to susceptibility to this subtype of glaucoma. The molecular mechanisms leading to angle closure glaucoma are largely unknown, but it is likely guided by underlying eye anatomy. Understanding genetic causes is the first step towards developing more effective treatments for preventing this condition. By studying a large family with angle closure and small eye size, we have recently identified a new candidate gene and mutation for this condition in a critical protein with an unknown role in eye development. This protein functions as a transcription factor regulating the expression of multiple genes in various organ systems. We hypothesize that dysfunction in this protein leads to abnormal eye development and in turn predisposition towards angle closure glaucoma. To test this, we will first evaluate the effect of our identified familial mutation on protein function. Next, we will identify the critical cells in the eye that express this protein during development. Finally, we will screen a cohort of individuals with small eyes and angle closure glaucoma for other mutations in this gene, and follow-up any candidate mutations with our established functional tests. These studies will establish the role of this regulatory protein in eye development and disease, and pave the path to investigate a new developmental pathway that leads to angle closure glaucoma.

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Teresa Puthussery, BOptom, PhD

UC Berkeley School of Optometry
Funded by Molly and David Pyott

Project: A Novel Approach to Assess Selective Ganglion Cell Vulnerability in Glaucoma

Summary: Glaucoma is a progressive blinding disease that leads to the death of ganglion cells, the nerve cells that transmit visual signals from the eye to the brain. There are many different types of ganglion cell in the human retina, each of which preferentially detects different features in the environment such as color, motion and fine spatial detail. This project will use a novel approach to determine whether specific types of ganglion cells are more prone to degeneration in human glaucoma. The results of this study will inform efforts to develop improved clinical tests for early detection and monitoring in glaucoma.

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Steven Roth, MD, FARVO

College of Medicine, University of Illinois
Funded by The Dr. Miriam Yelsky Memorial Research Grant

Project: Novel Slow-release Exosome Formulations for Glaucoma

Summary: Here we propose a new strategy for glaucoma, extracellular vesicles (EVs), which possess significant neuroprotective properties, linked to hydrogels for injection into the eye for prolonged EV delivery. Our aim is to develop and optimize EVs to provide neuroprotection for RGCs. The preparations will be tested and optimized using in vitro and in vivo models. This therapy using EVs fits the goals of precision medicine. EVs derived from mesenchymal stem cells (MSCs) have neuroprotective and regenerative properties and are well suited for glaucoma treatment. We will use specific binding peptides that recognize sites on the EVs to link them to alginate hydrogels. These EV/alginate preparations will be tested in vitro. In the second aim, we will test the efficacy of the preparations in a model of glaucoma. Well-developed methods including visual function and histology, and confocal imaging in vivo and in vitro will test efficacy of these EV modifications. The rationale is that medical or surgical intraocular pressure reduction, the only clinically approved glaucoma treatment, neither prevents the main pathophysiological mechanism, retinal ganglion cell (RGC) death, nor axonal loss. Administration route, dosage, and adverse effects limit clinical application of neuroprotective agents. Moreover, the complex pathology of glaucoma necessitates action upon multiple injury mechanisms, including oxidative stress, impaired axonal transport, neuro-inflammation, and excitotoxicity. Stem cells release EVs, nanoparticles that facilitate cell-to-cell communication. MSCs-EVs decrease neuronal cell death after hypox-ia/ischemia in vitro and in vivo, stimulate axonal growth, and attenuate inflammation and oxidative stress. They can be administered cross-species, and their stability, biocompatibility, biological barrier permeability, and low toxicity make them attractive therapeutic delivery vehicles. EVs are taken up by cells; unlike stem cells, which rely upon integration into tissues, or diffusion of secreted contents to the cells, EVs deliver their cargo directly. This study is significant because it will provide the first steps toward a precision therapy for glaucoma by advantageously harnessing properties of EVs and hydrogels, combined together for the first time.

Last reviewed on March 08, 2021

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