Research Results from Previous Years

Leonard A. Levin, MD, PhD, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

Project: Sustained-Release Formulations of Redox-Active Drugs for Neuroprotection in Glaucoma

Alexander C. Theos, PhD, Georgetown University, Washington, D.C.

Project: GPNMB Deficiency and Associated Cytotoxicity in Pigment Dispersion Syndrome, a Precursor of Pigmentary Glaucoma

Dr. Theos' research results will be published in an article titled "PKD Domains Distinguish PMEL and GPNMB Localization" in a 2013 edition of the peer-reviewed journal Pigment Cell & Melanoma Research. "This work would not have been completed without the support of the Glaucoma Research Foundation," Dr. Theos said.

Derek S. Welsbie, MD, PhD, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Project: Evaluating the Role of the c-Jun N-terminal Kinase Cascade in Retinal Ganglion Cell Death

Dr. Welsbie's research results were published in an article titled "Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death" in the March 5, 2013 edition of the peer-reviewed journal PNAS (Proceedings of the National Academy of Sciences).

David Andrew Feldheim, PhD, University of California Santa Cruz, Santa Cruz, California

Project: Transcriptional Control of RGC Health and Function

Purushottam Jha, PhD, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Project: Complement System as Therapeutic Target for Glaucoma

Melanie Kelly, PhD, Dalhousie University, Halifax, Nova Scotia, Canada

Project: Manipulating Lipid Signaling to Treat Glaucoma and Ocular Disease

Wei Li, PhD, University of Miami School of Medicine, Miami, Florida

Project: Global Mapping of Glaucoma Autoantibody Biomarkers

Rachel Wong, PhD, University of Washington, Seattle, Washington

Project: Exploring Loss and Recovery of Visual Receptive Field Properties in Populations of Retinal Ganglion Cells in a Glaucoma Model

William H. Baldridge, PhD, Dalhousie University, Halifax, NS Canada

Project: Calcium-permeable AMPA Receptors and Retinal Ganglion Cell Death during Glaucoma

Project Summary: "This study investigated the D-serine modulation of non-NMDA ionotropic glutamate receptors expressed by inner retinal neurons. To our knowledge, this is the first study to address specifically the effect of D-serine on AMPA ⁄ kainate receptors in intact central nervous system tissue, to identify its effect on calcium permeable AMPA receptors and to report the endogenous inhibition of AMPA ⁄ kainate receptors." - from the abstract of Dr. Baldridge's paper published in volume 35 of the European Journal of Neuroscience, 2012.

Hani Levkovitch-Verbin, MD, MPA, Goldschleger Eye Institute, Tel Hashomer, Israel

Project: Age-related Increased Vulnerability of Retinal Ganglion Cells to Elevated IOP- Mechanism and Neuroprotection.

Keith R. Martin, PhD, Cambridge Centre for Brain Repair, Cambridge, United Kingdom

Project: Pre-clinical Assessment of Human Retinal Ganglion Cell Neuroprotection by Human Stem Cells: Efficacy and Mechanism.

Eduardo J. Chichilnisky, PhD, The Salk Institute, La Jolla, CA

Project: Physiological Changes and Loss of Distinct Ganglion Cell Types in Glaucoma

Gareth R. Howell, PhD, The Jackson Laboratory, Bar Harbor, ME

Project: Understanding the Mechanisms of Wlds-mediated Protection in Glaucoma

Dr. Gareth Howell was awarded the 2013 Shaffer Prize for Innovative Glaucoma Research for his study investigating the mechanism by which a spontaneous mutation (Wallerian degeneration slow, Wlds) prevents retinal ganglion cell death in glaucoma. The Shaffer Prize recognizes the researcher whose project, funded by a Shaffer Grant in a given year, best exemplifies the pursuit of innovative ideas in the quest to better understand glaucoma.

Janice Vranka, PhD, Oregon Health & Science University, Portland, Oregon

Project: Versican as Primary Contributor to Aqueous Humor Outflow Resistance

Project Summary: Dr. Vranka’s project studied Versican, a large proteoglycan that is known to interact with many other proteins also present in the trabecular meshwork, which is thought to be the primary contributor to outflow resistance. Understanding of the overall structure and organization of the outflow resistance, which directly affects the intraocular pressure system will help to enable the development of better treatments to reduce pressure for primary open-angle glaucoma patients. Dr. Vranka’s findings were published in the July 2011 issue of Investigative Ophthalmology & Visual Science (IOVS).

Shunbin Xu, MD, PhD, Rush University Medical Center, Chicago, Illinois

Project: MicroRNAs in Retinal Ganglion Cells and Glaucomatous Neurodegeneration.

Emmanuel Buys, PhD, Massachusetts General Hospital, Boston, Mass.

Project: Soluble guanylate cyclase alpha 1-deficient mice: a novel murine model of elevated IOP and glaucoma

Tonia S. Rex, PhD, University of Tennessee Health Science Center, Memphis, Tenn.

Project: Systemic Delivery of a Neuroprotective Agent to Protect against Glaucomatous Cell Death in the DBA2/J Mouse

Project Summary: Dr. Rex was awarded the 2012 Shaffer Prize for Innovative Glaucoma Research for her research investigating the effectiveness of a neuroprotective therapy in a model of inherited glaucoma. Dr. Rex used gene delivery to provide long-term production of a modified form of erythropoietin (EPO), a hormone that induces red blood cell production but is also a neuroprotective cytokine. Gene delivery is ideal for glaucoma since it is a slowly progressing retinal degenerative disease. The Rex lab used the DBA/2J mouse model of pigment dispersion glaucoma. They treated prior to the onset of cell death, then monitored intraocular pressure and counted the number of surviving retinal ganglion cells.

Yi Zhao, PhD, Ohio State University, Columbus, Ohio

Project: Nanoengineered In Vitro Trabecular Meshwork ™ Model for Systematic Investigation of Aqueous Humor Outflow Resistance

Project Summary: This project developed an in vitro model using 3D porous polymer for studying the aqueous humor outflow in the eye. The results show that the in vitro model is a useful alternative to human donors because it allows parallel screening of a wide array of potent parameters that may regulate intraocular pressure. It provides a promising solution for unveiling the underlying mechanism of primary open-angle glaucoma and exploring effective therapeutics. Several proceeding papers and abstracts were published in conferences related to eye research and biomedical micro/nanotechnology, including the journals Biomedical Microdevices and Annals of Biomedical Engineering.

An Zhou, PhD, Robert S. Dow Neurobiology Laboratories, Portland, Oregon

Project: Epigenetic regulation of HIOP-induced endogenous neuroprotection in rat retinas

Project Summary: “In this GRF-supported study, we treated retinas with three related but different, high IOP-induced ischemic conditions: preconditioning (short ischemia, causing litter injury), injurious (prolonged ischemia, severe injury), and tolerant (preconditioning followed by prolonged ischemia, protected from injury). For retinas prepared from these three experimental conditions, we performed proteomic analyses using the latest technology so that proteins that are uniquely regulated under each condition can be identified. We then performed neuroanatomical analyses to validate proteomic findings and analyzed additional proteins that were suggested by proteomic findings. As a result, we report that, in ischemic-injured or ischemic-tolerant retinas, there is a striking difference in the abundance of a number of proteins that we know play important roles in neuroprotection against ischemic injury in brain. These proteins, if their roles in neuroprotection in the retina are fully established in the future by more comprehensive studies, may present novel therapeutic targets in treating retinal disorders including glaucomatous conditions.” Dr. Zhou's findings were published in the International Journal of Physiology, Pathophysiology and Pharmacology.

Haiyan Gong, MD, PhD, Boston University School of Medicine, Boston, Mass.

Project: A Study of the Dynamics of Schlemm's Canal Endothelial Cells using a Three-dimensional Cell Culture Device with Real-time Imaging. (Pictured at right: Dr. Gong examines samples using an electron Microscope).

Project Summary: "Schlemm's canal endothelial cells are believed to be one of the resistance sites crossed by the aqueous humor before entering the blood circulation and are likely to play an important role in the regulation of aqueous humor outflow resistance. In this study, we modified and applied a three-dimensional (3D) cell culture device which was recently developed at MIT to study the dynamics of Schlemm's canal endothelial cells. Our results demonstrated that our 3D cell culture device enables a real-time imaging of giant vacuole formation and tracers crossing the cultured endothelial cell monolayer in a controlled experimental condition. We showed that using a chemical, which can induce the cell into a more relaxed state, can promote giant vacuole formation. This result translates to an increase in drainage of aqueous humor and a decrease in pressure within the eye, similar to results established in animal models. This finding further validates our 3D cell culture devices as an experimental model for future glaucoma studies."

Deborah C. Otteson, PhD, University of Houston College of Optometry, Houston, Texas

Project: The Role of DNA Methylation in Regulating Eph Receptor Expression in the Retina

Dr. Otteson studied how retinal ganglion cells turn on and off the genes that regulate the normal patterns of connections during optic nerve development. Her overall aim was to enhance the development of regenerative therapies to restore the optic nerve and vision in glaucoma patients. She published the results of her findings in the September, 2010 edition of the journal Vision Research.

Paul Habib Artes, PhD, Dalhousie University, Halifax, NS, Canada

Project: Analysis of Progression in Glaucoma

Jamie Craig, PhD, Flinders University of South Australia

Project: Genome-wide Association in Primary Open Angle Glaucoma: The Blindness in Glaucoma Genetic Epidemiology Relative Risk Study

Brad Fortune, OD, PhD, Devers Eye Institute, Portland, Oregon

Project: Imaging the Course of Axonal Degeneration in Experimental Glaucoma

Kate E. Keller, PhD, Casey Eye Institute, Portland, Oregon

Project: RNAi Gene Silencing of Enzymes in the Glycosaminoglycan Biosynthetic Pathway

Dr. Keller was awarded the 2010 Shaffer Prize for Innovative Glaucoma Research for her research investigating the role of Glycosaminoglycans (GAGs) in fluid outflow resistance in the trabecular meshwork of the eye. Experimental results from this study could potentially lead to new therapies for lowering eye pressure in patients with primary open-angle glaucoma. Dr. Keller published her results in the scientific journals Investigative Ophthalmology and Visual Science and Experimental Eye Research.

Raquel L. Lieberman, PhD, Georgia Institute of Technology, Atlanta, Georgia

Project: Development of Pharmacological Chaperone Therapy for Inherited Primary and Juvenile Open Angle Glaucoma

Yutao Liu, MD, PhD, Duke University Medical Center, Durham, North Carolina

Project: Investigation of Gene Copy Number Variants in Primary Open Angle Glaucoma

"Thanks very much for your support of my research project in 2008. Your funding support initiated my CNV research program in POAG. With your funding, I then obtained further research funding from Duke Translational Research Institute in 2009 and American Health Assistance Foundation in 2010. Now I have published my research in PLoS ONE journal. Our work is the first to establish the potential connection between Krabbe disease and POAG. We found that GALC deletion could contribute approximately 1% of POAG cases. The GALC deletion carrier has 3-5 times more risk than a non-carrier."