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Glaucoma Research Foundation (GRF) provides seed money for creative pilot research projects that hold promise.
To date, we have awarded more than 200 grants to explore new ideas in glaucoma research. Known as “Shaffer Grants for Innovative Glaucoma Research” in honor of GRF founder Robert N. Shaffer, MD, 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 $40,000.
The 2016 research grants to explore new ideas are made possible through generous philanthropic support including leadership gifts from The Frank Stein and Paul S. May Grants for Innovative Research, The Alcon Foundation, the Dr. Henry A. Sutro Family Grant for Research, Dr. James and Elizabeth Wise, and the Melza M. and Frank Theodore Barr Foundation, Inc. Following is a summary of projects we are currently funding.
University of Miami Miller School of Medicine, Miami, FL
Funded by The Melza M. and Frank Theodore Barr Foundation, Inc.
Project: Axon-astroglial Interaction and its Effects on Optic Nerve Repair
Summary: Poor regeneration and reconnection of retinal ganglion cell (RGC) axons is a major obstacle for treating ocular trauma and diseases including glaucoma. There are as yet no therapies to repair optic nerve once the damage is done. Recent studies demonstrate that certain combinatorial treatments that modulate expression of multiple genes in RGCs promote long distance optic nerve regeneration. However, many regenerating axons have much trouble finding their original targets in the brain. Thus, it is critical to understand what factors contribute to the guidance defects. During development, astroglial cells (i.e. supporting cells of central nervous system) guide growing axons to their final destinations. In this study, we will examine whether glial cells and certain proteins secreted from these cells influence axon regeneration and guidance in the optic nerve in adult mice. In Aim 1, we generate cell specific-knockout mice and characterize deletion of expression of distinct genes relevant to axon guidance. In Aim 2, we will examine whether the rate and pattern of axon regeneration in these knockout mice are affected. Identifying factors that regulate directional growth of regenerating RGC axons to their targets will provide invaluable information on developing future therapies to repair degenerated optic nerve following glaucoma.
Johns Hopkins University, Wilmer Eye Institute, Baltimore, MD
Funded by Dr. James and Elizabeth Wise
Project: Neuroprotection through Altered Scleral Biomechanics
Summary: Glaucoma is a leading cause of irreversible blindness affecting over 60 million people worldwide. Currently, the only treatment option to prevent vision loss from glaucoma is reduction of intraocular pressure (IOP); however, adequate pressure lowering can be difficult to achieve, and even with significant pressure lowering, vision loss may continue. Efforts are underway to develop medications that inhibit vision loss additionally to IOP lowering, but no such medications are currently available. The outside wall of the eye (the sclera) plays an important role in determining how IOP changes cause vision loss in glaucoma. We have found that modifying the response of the sclera to IOP changes can prevent death of the cells that cause vision loss in glaucoma -- retinal ganglion cells (RGCs). In addition, we have found that specific medications used for treating high blood pressure alter the sclera's response to IOP changes and prevents death of RGCs. Treatment with blood pressure medications can cause systemic side effects such as dizziness, headaches, and drowsiness among others. In order to eliminate the chances of these side-effects, we have developed medications that can be delivered locally to the eye. In this proposal, we have designed experiments to test the efficacy of local medication delivery in preventing RGC loss in animal models of glaucoma. We will also further explore how these medications work by using mice that are missing important genes in the response to these drugs.
Washington University School of Medicine, St. Louis, MO
Funded by The Alcon Foundation
Project: Pathological Alterations in the Trabecular Meshwork Following Vitrectomy and Lens Extraction: A Model of Oxidative Stress
Summary: Elevation of pressure in the eye is the only risk factor for glaucoma that can be modified. Improved understanding of how the eye's natural drain is damaged can provide insights to new treatments and prevention of this blinding condition. We have measured oxygen levels inside the eyes of patients undergoing eye surgery with a small probe and found increased oxygen levels in patients who have had removal of the gel in the back of the eye, a procedure performed for various retinal diseases. Patients who have had this procedure nearly always require cataract surgery and this combination of procedures leads to an increased risk of glaucoma. This excess oxygen may be the source of molecules that cause damage to the cells of the natural drain of the eye. In addition, the level of antioxidants, compounds that protect the cells from this damage, are decreased following this combination of surgeries. By performing these two procedures (removal of gel and then lens removal), this will cause increased oxygen levels in the front of the eye in the area of the natural drain in a model of glaucoma. We will then examine these cells searching for proteins associated with damage and then study the how these cells may have altered programming of their genetic code. In this manner, we can learn more precisely how these cells are damaged and potentially identify patients who are at risk for damage and new ways to treat glaucoma.
Duke University Eye Center, Durham, NC
Funded by The Alcon Foundation
Project: Role of Exosomes in Glaucomatous Lamina Cribrosa Remodeling
Summary: The goal of this project is to discover changes in the eye that occur before the nerve damage that causes glaucoma. Nerve fibers exit the eye through a porous tissue called the lamina. In glaucoma, this tissue is compressed, reducing the space for both the nerve fibers and blood vessels that supply their nutrients. Though the precise mechanism is unclear, it is thought that these changes in the lamina are detrimental to the nerve fibers. The purpose of this proposal is to investigate the role of small vesicles called exosomes in lamina remodeling resulting from mechanical stress. Our proposed experiments simulate the forces experienced by cells in the lamina in two ways. In the first model, cells grown on a flexible material are stretched. This simulates the forces they experience prior to and during glaucoma due to high pressures in the eye. These forces have been shown to alter cell biology and how cells remodel the laminar tissues. In glaucoma patients, the lamina is reported to be softer than in non-glaucomatous patients. The second model simulates the effect of a softer lamina by growing cells on silicone with different stiffness. Cells sense the material softness and often activate pathways to make it even softer. This would make the tissue more compressible and the problem worse for the nerve fibers. By examining the exosomes released by these cells under the different conditions, we hope to identify 1) the cell biology that leads to nerve damage and glaucoma and 2) biomarkers to predict glaucoma susceptibility.
Edward Hines, Jr. VA Hospital, Hines, IL
Funded by The Alcon Foundation
Project: Mitochondrial-specific Antioxidant XJB-3-151 as a Novel Therapeutic Strategy to Lower Elevated Intraocular Pressure
Summary: Patients with primary open-angle glaucoma (POAG) often present with chronically elevated intraocular pressure (IOP), the result of increased resistance to aqueous humor outflow through the trabecular meshwork. While the cause of changes in aqueous humor outflow resistance remain unclear, it has been established that the amount of transforming growth factor-beta2 (TGF-Î²2) is increased by 60-70% in the aqueous humor of POAG patients. TGF-Î²2 is known to elevate IOP by promoting increases in aqueous humor outflow resistance through the trabecular meshwork. However, no currently-available treatment options alter endogenous TGF-Î²2 expression. Our lab has recently shown that endogenous TGF-Î²2 expression can be markedly and significantly attenuated in human trabecular meshwork cells and porcine anterior segments using the compound XJB-5-131, a novel antioxidant that targets a cell's mitochondria. Here, we hypothesize that XJB-5-131 will lower IOP by decreasing endogenous TGF-Î²2 gene expression and protein secretion. By lowering expression and release of TGF-Î²2, a protein that is known to elevate IOP, we believe that XJB-5-131 may present as a new treatment option for POAG patients with poorly-controlled elevated IOP.
Co-investigator: Louis R. Pasquale, MD
Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
Dr. Henry A. Sutro Family Grant for Research
Project: Estrogen & Glaucoma
Summary: We hypothesize that early estrogen deficiency accelerates optic nerve aging and predisposes this nerve to glaucomatous damage. We further hypothesize that estrogen administration may remove these risks and serve as a novel preventive treatment for glaucoma. Estrogen deprivation has been linked to an increased risk of developing glaucoma. In addition, estrogen use may decrease the risk of developing glaucoma, prevent retinal ganglion cell death, reduce intraocular pressure and preserve visual acuity. However, despite these impressive results, there is no global consensus on the role of estrogens in glaucoma. Indeed, there is significant controversy. It is extremely important to determine the role of estrogen. The reason is that estrogen dynamics may play a major role in the increased prevalence of angle closure glaucoma in women, and may contribute significantly to the development of primary open-angle glaucoma in women and possibly men. Further, there is an ever-increasing use of aromatase inhibitors for the treatment of breast and ovarian cancer. These inhibitors prevent the biosynthesis of estrogens and could enhance the risk and/or severity of glaucoma.
Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA
Project: Endocannabinoids in Retinal Ganglion Cell Regeneration
Summary: Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive destruction of neural connections between retinal ganglion cells and the brain. Loss of these neural connections is generally understood to be irreversible. However, emerging evidence suggests that adult retinal ganglion cells may sometimes be coaxed to behave in a manner similar to that observed during embryologic development, when neural connections are normally formed. Understanding molecular mechanisms that govern the growth of connections between retinal ganglion cells and the developing brain may ultimately lead to new regenerative therapies for patients with glaucoma. We are investigating the functions of lipid messenger molecules called endocannabinoids. These molecules facilitate growth of certain developing neural connections, but the actions of endocannabinoids on retinal ganglion cells are unknown. We are using an advanced mass spectrometry-based molecular imaging technology to define the spatial distribution of endocannabinoids within the part of the retinal ganglion cell responsible for establishing a connection with the brain: its axon. Our hypothesis is that endocannabinoids are enriched at high concentration within tips of the growing axons. If this is correct, it would suggest that retinal ganglion cell axons synthesize endocannabinoids to stimulate their own growth. It would also implicate the endocannabinoid system as a potential therapeutic target to facilitate regeneration of neural connections destroyed by glaucoma.
University of California, San Diego
Project: Development of an Optical-based Intraocular Pressure Sensor
Summary: Glaucoma is an incurable eye disease affecting over 60 million people worldwide. As primary risk factor for glaucoma, elevated intraocular pressure (IOP) is often associated with optic nerve damage and loss of vision. Current standard glaucoma care involves doctor visits in which patients' eye pressure is measured using a device known as a tonometer. Tonometric examinations, however, are infrequent and insufficient as they are only able to provide single point measurements of the patient's IOP, which can fluctuate over time. Without adequate pressure information to fully characterize the pressure profile, ineffective treatments and care could unknowingly cost patients their vision. Thus, there is a pressing need for continuous IOP monitoring to improve glaucoma management and treatment. The Talke Lab at UC San Diego is developing a novel implantable IOP sensor to address this unmet need in glaucoma care. The sensor can be integrated with the intraocular lens and surgically inserted in the eye through cataract surgery. The technology allows monitoring of IOP on a regular basis at the convenience of the patients' home or office. Eye pressure measurements obtained from the sensor can significantly improve the way eye doctors are diagnosing and treating their patients. With the data obtained, target eye pressure can be established for individual patients and treatment plans can be adjusted to achieve therapeutic goals. Personalizing the management of glaucoma care would be an innovation and a major landmark advance in ophthalmology.
Last reviewed on October 29, 2017
This article appeared in the May 2016 issue of Gleams.Subscribe