Yvonne Ou, MD
Assistant Professor of Ophthalmology, University of California, San Francisco
Research: “Early steps of circuit disassembly in glaucoma”
Research
Early steps of circuit disassembly in glaucomaGlaucoma is a degenerative optic neuropathy characterized by a gradual loss of peripheral vision that may go undetected until the disease is at a very advanced stage and involves central vision. The underlying cause of vision loss and disability in glaucoma is the progressive loss of retinal ganglion cells (RGCs). Once RGC death occurs, the visual field loss incurred is irreversible, and continuation of the disease process can lead to blindness.
We are interested in understanding the earliest steps of ganglion cell degeneration, and whether there are particular ganglion cell types and circuits that may be more vulnerable in glaucoma. Although we know that these RGCs are injured in glaucoma, we do not yet understand the steps between ganglion cell injury and death, nor do we know how other cell types in the retina are affected by elevated intraocular pressure (IOP). A detailed understanding of the earliest changes that occur will allow us to design treatments that can rescue RGCs before irreversible cell death occurs.
To this end, we are examining the initial steps of circuit disassembly after IOP elevation. Our previous work has shown that alterations to excitatory synapses in the OFF sublamina of the inner plexiform layer of the retina are among the earliest events occurring after acute IOP elevation, accompanied by selective dysfunction of OFF RGCs, dendritic morphologic changes, and greater cell death. Therefore, we seek to understand whether inputs to the ON vs. OFF RGCs are differentially affected. Understanding the steps of circuit disassembly and the mechanisms underlying the “selective vulnerability” of different RGC types and retinal circuits will advance the field by providing new targets for diagnosis and treatment, as well as fundamentally improve our understanding of how circuits react and rearrange in the face of injury.
