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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 2018 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, Edward Joseph Daly Foundation, and the R. David Sudarsky Charitable Testamentary Trust. Following is a summary of projects we are currently funding.
University of Tennessee Health Science Center
Project: Extended Release IOP-Lowering Formulation
Summary: The leading cause of irreversible blindness in the world is glaucoma, and 90% of all glaucoma cases present as primary open angle glaucoma (POAG). An elevated intraocular pressure (IOP) most often is a significant risk factor for vision loss in this disease. Treatment of POAG is a major challenge because there are many reasons for vision loss and current therapies require a patient to instill eye drops several times per day. Our recent work has identified a new gene that directly modifies IOP. In this study, we are testing a drug that binds to the protein encoded by this gene. We are also designing a new eye drop that will require only a single drop per day to maintain IOP at low levels throughout the day. Our success in this endeavor would represent a major contribution to the understanding and treatment of glaucoma.
Oregon Health & Sciences University
Project: Trabecular Meshwork Stem Cells and the Identification of the Laser Factor
Summary: The principal risk for glaucoma is persistently elevated intraocular pressure. The cells that regulate this pressure in the eye are trabecular meshwork cells, but with glaucoma, many of these cells have died or are not functioning properly. What is needed is to increase the number of these cells to restore function to these trabecular meshwork cells, so that they may once again regulate the pressure to normal. One of the commonly used treatments for glaucoma, laser trabeculoplasty, increases the production of a factor that is instrumental in increasing cell division and cell replacement. Our long-range goal is to develop methods that facilitate the use of this laser factor, which increases cell division in trabecular meshwork cells after laser treatment, as a novel treatment for glaucoma. We can identify this factor by standard laboratory methods, and then determine a molecule that stimulates the biochemical pathway to cell division. These studies will allow us to identify the factor produced by trabecular meshwork cells after laser treatment which initiates restorative cell division, and provides an approach to develop a stimulatory molecule to increase cell division without laser or surgical treatments. This study has potential to initiate an improved glaucoma treatment to regulate intraocular pressure and delay or prevent glaucoma.
University of Utah
Project: Regulation of Tensile Homeostasis in the Trabecular Meshwork
Summary: This project investigates two crucial aspects of pressure regulation in trabecular meshwork cells. First, it tests the novel idea that the response of trabecular meshwork cells to pressure is continuously modulated by a dynamic balance between pressure-sensitive activating (TRPV4) and deactivating (TREK1) ion channels. The latter are critical to compensate for the transient increases in pressure seen in healthy eyes whereas glaucoma would result from overactivation of TRPV4 or downregulation of TREK1. The second aim tests the idea that prolonged exposure to pressure-dependent TRPV4 activation recruits additional types of ion channels, which critically contribute to chronic pathological remodeling. The experimental approach is based on state-of-the-art methods adopted from current mechanobiology that have never been used in ocular context. Overall, the project aims to resolve the longstanding knowledge gap about the mechanisms that mediate trabecular pressure sensitivity, thereby allowing for the development of novel targeting strategies to reduce intraocular pressure.
University of California, San Francisco
Project: Ganglion Cell Dysfunction in Glaucoma
Summary: Glaucoma is an irreversible blinding disease in which the cells that comprise the optic nerve, the retinal ganglion cells (RGCs), are damaged and die. A major gap in taking care of glaucoma patients is that we do not have an objective test that measures how well the RGCs are functioning. There are actually over 30 types of RGCs, and our laboratory has recently identified specific types of RGCs that are more vulnerable in glaucoma. Taking advantage of this knowledge, we are developing novel methods to assess the function or health of RGCs that are more vulnerable versus more resistant to damage. A more sensitive and objective test of RGC function and health will greatly improve our ability to take care of glaucoma patients and their vision.
Case Western Reserve University
Project: Anti-fibrogenic Matricellular Protein CCN1 as a Novel Therapeutic Target to Lower Intraocular Pressure
Summary: Primary open-angle glaucoma is a form of glaucoma characterized by elevated intraocular pressure (IOP). A rise in IOP above normal is a major risk for glaucoma with significant consequences on vision and quality of life. Lowering IOP is the most effective way to delay the onset of glaucoma, and halt the progression towards vision loss. A reduction of IOP by 20% decreases the risk of developing glaucoma in patients with elevated IOP. High pressure in the eye is due to the decreased removal of aqueous humor through the trabecular meshwork. Changes in the cell-cytoskeleton interactions can alter the accumulation of protein materials that provide extracellular structural and biochemical support called the extracellular matrix in the drainage pathway. This can increase the IOP. We have identified a protein called CCN1, which decreases the formation of the actin fibers and the extracellular matrix. We believe that CCN1 acts via proteins called integrins, to bring about the changes in actin and extracellular matrix. This project aims at understanding the function of CCN1 in the aqueous humor drainage pathway.
University of Maryland
Project: Noncontact Mechanical Mapping of the Optical Nerve Head with Brillouin Microscopy
Summary: Growing evidence suggests that glaucoma development is linked to how the tissues at the back of the eye respond to intraocular pressure (IOP) mechanically, i.e. how much they can resist to be strained when IOP increases. However, our understanding of this phenomenon is poor because no current technology can assess the stiffness (i.e. the resistance to deformation) of the sclera and neural tissue without dissecting the eye. To address this need, this proposal will develop and test an optical technology, Brillouin microscopy, which can image stiffness without contact. With this novel technology, we will measure stiffness changes of sclera/neural tissues in glaucoma vs. healthy eyes. This pilot grant will provide a new tool to diagnose eyes at risk of glaucoma based on their stiffness properties and to monitor new treatments that are currently being proposed based on changing the stiffness of the sclera/neural tissues.
University of California, San Diego
Project: Eliminate to Protect
Summary: Glaucoma is a group of optic neuropathies characterized by slow, progressive loss of retinal ganglion cells (RGCs), degeneration of the optic nerve and, consequently, loss of vision. Although the main risk factors associated with the development of the disease are elevated intraocular pressure and aging, genetic studies have described a number of loci in the genome that further increase the risk of glaucoma. Despite extensive efforts, the molecular impact of each locus on the pathogenesis of glaucoma and its influence on retinal ganglion cells (RGCs) biology is not well understood. In our project, we propose to investigate whether the removal of early senescent RGCs in glaucomatous eyes will protect neighboring RGCs from cell death. We hope to provide solid foundation for future studies on potential applications of senolytic drugs in glaucoma patients.
Baylor College of Medicine
Project: Elucidating the Dynamics of the Neuronal Stress Response in Driving the Death of Retinal Ganglion Cells
Summary: The Dual Leucine-zipper Kinase (DLK) is an attractive target for glaucoma therapy. DLK is a key activator of the “neuronal stress response” that is engaged during retinal disease, and prolonged DLK activation can result in neuronal death. Blocking DLK prevents the slow and steady loss of retinal neurons in models of glaucoma, suggesting that small molecule inhibitors of DLK may help to save neurons and preserve vision in human disease. Paradoxically, the activity of DLK is not only detrimental in glaucoma but also drives regenerative signaling that may be essential for therapeutic strategies to restore lost vision. The successful development of therapeutic strategies targeting DLK will therefore depend on identifying the patterns and levels of DLK activity that allow it to support repair strategies without inducing neuronal death. The proposed study utilizes a drug-inducible form of DLK to determine which types and timing of DLK activity result in the loss of retinal neurons. We aim to identify the “sweet spot,” also known as the therapeutic window, in which regenerative signaling is preserved but neuronal death is minimized. This information is essential for identifying target levels of DLK inhibition or stimulation in both neuroprotective and neuroregenerative strategies.
Last reviewed on March 13, 2018