Understanding the Earliest Steps of Optic Nerve Cell Death in Glaucoma

Yvonne Ou, MD
University of California, San Francisco
Year Awarded:
2016
Grant Duration:
July 1, 2016 to June 30, 2018
Disease:
Glaucoma
Award Amount:
$150,000
Grant Reference ID:
G2016084
Award Type:
Standard
Award Region:
US Northwestern

The Douglas H. Johnson  Award for Glaucoma Research.

Yvonne Ou, MD

Retinal Synapse Disassembly in Glaucoma

Summary

In glaucoma, the cells of the optic nerve die and that can lead to blindness. Although we know that optic nerve cells are injured in glaucoma, we do not yet understand the steps between optic nerve cell injury and death. A detailed understanding of the earliest changes that occur will allow us to design treatments that can rescue these injured optic nerve cells before irreversible cell death occurs.

Details

Our goal is to understand the earliest steps of injury to the optic nerve cell, or retinal ganglion cell (RGC), in glaucoma. In glaucoma, the cells of the optic nerve die and can lead to blindness. Although we know that these RGCs are injured in glaucoma, we do not yet understand the steps between optic nerve cell injury and death; nor do we know whether other cell types in the retina are also affected by elevated intraocular pressure. A detailed understanding of the earliest changes that occur will allow us to design treatments that can rescue these injured optic nerve cells before irreversible cell death occurs.

Our laboratory is focused on how RGCs degenerate in glaucoma in order to improve diagnosis and treatment of this disease. The retina is composed of multiple layers of interconnecting nerve cells, with the RGC being the final “output” nerve cell, or neuron, that transmits all of the light information received by the retina to the brain where it is processed. We are identifying some of the earliest changes in the retina, specifically at the synapses, which connect RGCs with their partners. Synapses are the connections where information from one neuron passes to another. In the case of the RGC, it receives information via synapses from bipolar cells, another type of neuron. A second goal of this project is to understand whether the bipolar cells are responding to elevated eye pressure and altering their synapses in response. Finally, recent studies have highlighted the importance of components of the immune system, specifically complement, in tagging these damaged synapses for elimination. We will study whether these components are increased in the specific cells that are most prone to injury from glaucoma.

Our investigations are innovative because understanding how these connections, or synapses, are affected in glaucoma is relatively unexplored territory. Knowing the precise effects of glaucoma on the synapses between RGCs and bipolar cells will open up new avenues for designing better diagnostic tests, where we can catch and track the progression of the disease earlier, before optic nerve cells die. In their case, death is irreversible; unlike some other cells in the body, optic nerve cells are not capable of regenerating.

This project will also open new avenues for treatments, as stabilizing synapses is potentially a target for which one could design medications. Additionally, if cell transplantation were to be pursued as a treatment for glaucoma, it would be important to understand how the remaining circuitry of the eye behaves in glaucoma, as these transplanted cells would need to be able to form appropriate connections with partner cells.

About the Researcher

Dr. Yvonne Ou is a board certified ophthalmologist who specializes in glaucoma. Her research interest is in the area of glaucoma neurodegeneration, and she has dedicated her efforts towards the goal of developing new diagnostics and therapies. At UCSF, Dr. Ou is testing a novel hypothesis that retinal synapse loss occurs early in the glaucoma disease process, and that certain types of retinal ganglion cells may be more vulnerable to elevated eye pressure compared to other types. Dr. Ou’s overall goal is to elucidate diagnostic and therapeutic targets earlier in the course of the disease and translate these findings to help improve the vision and quality of life of glaucoma patients.

After majoring in biochemistry at Harvard College, Dr. Ou earned her medical degree from Harvard Medical School and completed her residency in ophthalmology at the Jules Stein Eye Institute, UCLA. She has completed both clinical and research fellowships in glaucoma at Duke University.

Personal Story

As a glaucoma clinician-scientist, the number one question my patients ask me is, “What can I do to help slow the progression of my disease?” It is frustrating that our current options all involve eye pressure lowering. This is obviously important, but I am motivated by the fact that we need better ways of tracking glaucoma progression and of treating it. When I was an ophthalmology resident deciding what subspecialty to enter, I saw a large need for glaucoma researchers, and I also was drawn to the fact that glaucoma specialists form life-long relationships with our patients. It is my hope that during my career I not only help patients in the clinic and the operating room, but also make scientific and clinical advances in our field. I am immensely grateful to the BrightFocus donors for making these grants possible, because without them, many of our early innovative ideas could not get the traction needed to become competitive for larger grants from the National Institutes of Health and other funding institutions.

I am an avid runner who loves the open spaces one can find in the city of San Francisco, and in fact I met my husband through running. As a relatively new mother of two children, I have gained new appreciation for seeing the world through fresh eyes, and it is my hope to translate this by bringing new and fresh ideas to the field of glaucoma.

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