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Hui Chen, Yan Zhao, Liang Feng, Jianhua Cang, John Troy, Xiaorong Liu; Functional Degeneration of Retinal Ganglion Cells in a Mouse Model of Chronic Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2013;54(15):795.
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Glaucoma, characterized by dendritic and axonal degeneration of retinal ganglion cells (RGCs), visual field deficits, and ultimately RGC death, is one of the leading causes of blindness in the US. Although diversity in RGC damage has been reported in glaucomatous retinas, studies in human patients and animal models have so far failed to provide a clear picture of how RGCs degenerate and whether the surviving RGCs are still functional. In this study, we examined the functional degeneration of RGCs in a mouse model of experimental glaucoma.
We have adopted a laser-induced mouse model of ocular hypertension to mimic human high-tension glaucoma and demonstrated a sustained increase of intraocular pressure (IOP), and a progressive RGC loss. We applied two cutting-edge techniques, the laser-guided focal electro-retinogram (ERG) to measure visual responses from different retinal cell types at various locations, and a large-scale multi-electrode array (MEA) to examine response properties of different subtype RGCs. We classified RGCs into ON, OFF and ON-OFF subtypes by using the innovative variant of Spike Triggered Covariance (STC) analysis, STC-NC (Cantrell et al., 2010). We compared the response properties of different subtypes of RGCs from hypertensive eyes and age matched controls. We further divided the retina into four quadrants (superior, inferior, temporal and nasal) and examined whether RGCs from different locations of the retina respond differently to the insult of ocular hypertension.
We recorded the visual responses of RGCs from laser-treated right eyes and compared with untreated left eyes. Our preliminary data suggest that at 6 weeks after laser treatment there were more ON cells and fewer OFF cells while the percentage of ON-OFF cells remained unchanged. The receptive field (RF) sizes of mono-laminated ON and OFF RGCs decreased while the bi-laminated ON-OFF RGCs did not change in the glaucomatous eyes.
RGCs degenerate in a subtype- and location-dependent manner in ocular hypertensive mice. This study establishes a valuable model system with which to better understand how RGC degeneration leads to vision loss and a potential time window for early detection of glaucoma.
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