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Yvonne Ou, Ming Lu, David Sretavan, Erik Ullian; Global assessment of retinal ganglion cell synapses in a mouse model of ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2013;54(15):773. doi: https://doi.org/.
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Glaucoma is a neurodegenerative disorder characterized by retinal ganglion cell (RGC) loss with optic nerve cupping and visual field defects. Disease mechanisms are not well understood, but evidence suggests that the pathological degeneration of a stressed RGC is compartmentalized at the subcellular level, with changes in the synaptic, dendritic, and axonal compartments. The purpose of this study is to determine the effects of laser-induced ocular hypertension (LIOH) on excitatory synapse number in the inner plexiform layer of the retina.
Intraocular pressure (IOP) was elevated unilaterally using laser photocoagulation of the limbal and episcleral vessels of adult CD-1 mouse eyes. IOP was measured by rebound tonometry. Retinas were dissected and prepared for whole-mount retina immunohistochemistry using PSD95 to label excitatory postsynaptic sites of RGCs in the inner plexiform layer. Brn3a was used to label RGCs in the ganglion cell layer.
After laser-induced ocular hypertension (LIOH), the IOP of the treated eye was elevated as early as 6 hours and returned to baseline by 1 week. Two months after LIOH, in areas of RGC loss there was concurrent synaptic loss as measured by PSD95 immunostaining. Interestingly, when synaptic puncta were quantified in areas of similar RGC density of the treated eye as compared to the control eye, there was also statistically significant synapse loss.
Excitatory synapse loss occurs concurrently with RGC degeneration in this mouse model of ocular hypertension. However, even in areas of relative preservation of RGCs as measured by RGC soma marker Brn3a, there was significant synaptic loss in the treated eye, suggesting that synapse loss is an early event in glaucomatous RGC degeneration.
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