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2019 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 2019 research grants are made possible through generous philanthropic support including leadership gifts from the Frank Stein and Paul S. May Grants for Innovative Glaucoma Research, the Dr. Henry A. Sutro Family Grant for Research, Dr. James and Elizabeth Wise, The Dr. Miriam Yelsky Memorial Research Grant, Roberta and Robert H. Feldman, Carolyn and Richard Sloane, and the Edward Joseph Daly Foundation. Following is a summary of projects we are currently funding.


The 2019 Shaffer Grants for Innovative Glaucoma Research


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Steven Barnes, PhD

Doheny Eye Institute
Funded by Roberta and Robert H. Feldman

Project: Functional Resilience of Retinal Ganglion Cells During Mitochondrial Dysfunction

Summary: Optic neuropathies result from metabolic dysfunctional states, wherein the retinal ganglion cells fail to meet the energy demands upon them to maintain health and functionality. This energy failure occurs in response to several factors, some being of genetic origin while others arise from environmental factors including plasma leakage and axonal damage. As a result of the failure of a neuron to maintain energy sufficiency, deficits in electrical signaling occur characterized principally by reduced intrinsic excitability. This is expressed in the damaged neuron as failure to maintain a negative resting voltage and abnormal action potentials. Both contribute to excess Ca2+ loads within the cells, which induce apoptosis and necrosis. This project aims to resolve the longstanding knowledge gap about the specific mechanisms that mediate failures of intrinsic excitability, with the goal of aiding novel strategies that reduce energy failure and restoring energy production. Sensitive and objective tests relating ganglion cell function to their bioenergetic health will greatly improve our ability to detect and ameliorate ganglion cell degeneration in the early stages of optic neuropathies, such as glaucoma, extending vision for glaucoma patients.


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Adnan Dibas, PhD

North Texas Eye Research Institute
Funded by the Edward Joseph Daly Foundation

Project: Endothelin Converting Enzyme Knockdown is Neuroprotective in Glaucomatous Neuropathy

Summary: Very little is known about how and why the optic nerve is progressively damaged in glaucoma, a leading disease for blindness worldwide. Conditions known to cause glaucoma such as elevated intraocular pressure, hypoxia, and ischemia were found to be associated with changes in the expression of aquaporin water channels in non-ocular tissues (e.g. brain, neurons, and muscle). Conditions known to cause glaucoma such as elevated intraocular pressure are associated with increased small proteins known as endothelins. Data obtained in the current study suggests that elevation of IOP in rats resulted in the activation of endothelin-producing enzymes known as ECE. Therefore, reduction of ECE activities may be a novel therapeutic in the treatment of glaucoma. Currently glaucoma medication involves only pressure lowering medication, however, vision loss continues. Therefore, the identification of additional mechanisms that continue to promote vision loss will assist in the development of combination therapy of lowering pressure and preventing vision loss in glaucoma.


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Ankur Jain, PhD

University of Iowa
Funded by The Dr. Miriam Yelsky Memorial Research Grant

Project: Autophagy-targeted Treatment for Myocilin-associated Glaucoma

Summary: Glaucoma is a leading cause of irreversible blindness worldwide affecting approximately 80 million individuals. Elevated intraocular pressure (IOP) is the most important and the only modifiable risk factor associated with glaucoma. Trabecular meshwork ™, present at the junction of iris and cornea, regulates aqueous humor outflow and IOP. Mutations in myocilin (MYOC) gene are responsible for a subset of primary open-angle glaucoma. These gain-of-function mutations result in non-secretion of MYOC, ER stress in TM and elevated IOP. The overall goal of our research is to study how TM cells handle this accumulating mutant protein in MYOC-associated glaucoma. Our group has previously shown that reducing MYOC load intracellularly, either chemical or genetic intervention, relieves glaucoma phenotypes in mice. Autophagy is an important cellular homeostatic mechanism to a number of cytotoxic stress. We propose to study the role of autophagy in clearing out mutant myocilin protein in TM cells and relieving elevated IOP phenotype and optic nerve damage in our transgenic mouse model. Results from this study will define the direct role of autophagy in clearing intracellular mutant MYOC protein in glaucoma and will open a door to new targets for glaucoma therapy.


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Pierre Mattar, MSc, PhD

Ottawa Hospital Research Institute
Funded by Carolyn and Richard Sloane

Project: Programming and Reprogramming for Retinal Ganglion Cell Replacement Therapy

Summary: Although Glaucoma is frequently treatable with medication or surgery, a large proportion of afflicted individuals are diagnosed too late to prevent the death of retinal ganglion cells (RGCs). As RGCs are the only neurons that transmit information from the eye to the brain, their loss results in permanent vision impairment. Although RGCs cannot be naturally regenerated, they can be produced artificially from retinal stem cell cultures. This strategy thus offers the promise of recovery for vision loss. However, in order to bring this approach to the clinic, we will need to greatly improve our ability to produce these cells efficiently. We propose to use genetic modification to force retinal stem cells to generate RGCs efficiently, using factors that have been shown to perform this function during the natural development of the eye.


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Lauren Katie Wareham, PhD

Vanderbilt University Medical Center
Funded by Dr. James and Elizabeth Wise

Project: Investigating the Role of the NO-GC-1-cGMP Signaling Pathway in Glaucoma

Summary: Glaucoma is an optic neuropathy characterized by the loss of neuronal cells in the retina (retinal ganglion cells; RGCs). RGCs and their projections form the optic nerve, so loss of these cells in glaucoma leads to irreversible vision loss. Elevated intraocular pressure (IOP) is currently the only target for glaucoma therapy, but this therapy often serves only to slow progression of the disease, not cure it. Therefore, there is a need for new therapies that target RGCs at the back of the eye. The nitric oxide signaling pathway has been highlighted as a novel pathway that is important in glaucoma disease progression. Guanylate cyclase is an enzyme that is activated by nitric oxide, which in turn produces cyclic-guanosine monophosphate (cGMP), an important signaling molecule. It has been shown that this pathway has roles in maintenance of IOP and also in neuroinflammation. It is known that the GC-1-cGMP pathway modulates neuroinflammatory pathways such as those implicated in glaucoma. However, the potential mechanism of this activity has not yet been investigated. In this proposal we aim to determine how the GC-1-cGMP pathway is involved in the modulation of these neuroinflammatory pathways, and then we can determine whether targeting these neuroinflammatory pathways could enhance protection of RGCs.


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Pete A. Williams, PhD

Karolinska Institutet (Stockholm, Sweden)
Funded by the Dr. Henry A. Sutro Family Grant for Research

Project: Targeting Neuronal Mitochondria for Neuroprotection in Glaucoma

Summary: Although there are tactics in the clinic to alleviate high eye pressure in glaucoma, there are no strategies that target the optic nerve. Thus, therapeutic tactics that target the retina and optic nerve are of great therapeutic need. I have recently discovered a role for nicotinamide (a form of vitamin B3) in protecting the optic nerve in glaucoma by targeting metabolic processes that change in the retina early during glaucoma. Nicotinamide is well tolerated, inexpensive, and robustly protective and thus may be an ideal therapeutic candidate for glaucoma patients. I will focus my research on these metabolic changes within neurons to discover therapeutic strategies in animal models that can be translated to human patients in the clinic. We will further test additional molecules that work through the same pathways as nicotinamide. To aid in this we have developed glaucoma models that will allow us to accurately assess mitochondrial changes in retinal ganglion cells (the primary output neuron of the retina, whose axons make up the optic nerve), and assess the effects of treatments on these cells. My research group prioritizes compounds and gene therapies that have well-established human safety profiles and as such could go straight into clinical use.


The 2019 Frank Stein and Paul S. May Grants for Innovative Glaucoma Research


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Daniel M. Lipinski, PhD

Medical College of Wisconsin

Project: Development of rAAV Vector Technologies to Facilitate Topical Gene Delivery to the Cornea

Summary: Vision loss in glaucoma occurs due to degeneration of retinal ganglion cell axons due to chronic ocular hypertension. Current treatment strategies focus on lowering intraocular pressure (IOP) to either decrease aqueous production or increase aqueous outflow by promoting uveoscleral drainage. Pharmacological approaches can be effective at lowering IOP, but they are often undermined by poor patient compliance, with a recent study finding that 50% of patients fail to administer treatment 75% of the time. Up to 90% of patients require adjunctive therapy within their lifetime in order to manage their condition. We have previously established that rAAV-mediated expression enzymes that manufacture prostaglandins from the cornea results in a highly significant reduction in IOP in normotensive mice that is sustained for several months. Current delivery strategies, however, necessitate that the rAAV vector is injected into the anterior chamber of the eye, greatly increasing the risk of developing complications that may exacerbate vision loss in patients with glaucoma. In this proposal we will explore non-invasive methodologies for the delivery of genetic material to cells of the cornea using a contact lens-based approach. It is our expectation that a contact lens-based delivery technology will substantially increase clinical translatability of the proposed gene therapy by reducing invasiveness.


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Biraj Mahato, PhD

University of North Texas Health Science Center

Project: Chemically Reprogrammed Retinal Ganglion Cell Therapy to Treat Glaucomatous Neuropathy

Summary: Retinal ganglion cells (RGCs) are the neurons that transmit light signal from the eye to the brain and so that we can see. Even when rest of the visual system is healthy, if RGCs are dead or dysfunctional, vision is impossible. RGCs are primarily damaged in glaucoma with its attendant elevated eye pressure and once damaged they fail to regenerate, leading to irreversible blindness. Embryonic stem cells or induced pluripotent stem cells are promising tools to replace RGCs. However, the protocol to obtain such cells are cumbersome and time consuming. There are many hurdles and challenges that have yet to be overcome, such as tumor growth, time and labor-intensive manufacturing processes, and political and ethical controversies, forcing scientists to search for alternate strategies. In an exciting discovery we have identified a set of five small molecules that can reprogram human skin fibroblasts to retinal ganglion cells. Our method demonstrates a safe, effective, and efficient source of RGC replacement cells to restore vision, without the use of embryonic or pluripotent stem cells. In depth molecular analysis of chemically converted RGCs and exploring their prospective function in a rodent model carries extraordinary translational potential for millions of visually impaired glaucoma patients worldwide.

Last reviewed on March 14, 2019

This article appeared in the March 2019 issue of Gleams.

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