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Yang Zhang, Ashish Bhandari, Andrew Stothert, Jennie C. Smith, Matthew J Van Hook; All classes of melanopsin-expressing retinal ganglion cells are protected from degeneration in early ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2019;60(9):648.
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© ARVO (1962-2015); The Authors (2016-present)
Recent studies suggest that melanopsin-expressing retinal ganglion cells (RGCs) might be more resistant to ocular hypertension (OHT)-induced injury. To test this possibility, we examined the effects of OHT on cellular degeneration of RGCs in an experimental mouse model of glaucoma.
Bilateral anterior chamber injection of 10-micron microbeads was used to modestly increase intraocular pressure (IOP) of 6-8 weeks old Opn4-Cre;Ai32 mice, which express channelrhodopsin-2/YFP in the six known classes of melanopsin-expressing RGCs (M1-M6); control mice were injected with sterile saline. After 5 weeks, retinas were harvested, mounted on nitrocellulose membranes and fixed in PFA. YFP in melanopsin-expressing RGCs was enhanced by staining with an anti-GFP antibody; total RGCs were separately labeled with an anti-RBPMS antibody. Retina location was established by staining for S-opsin, which is expressed in a dorsal-ventral gradient in cones. RGCs in the ganglion cell layer were then imaged on 2-photon microscope, and RGCs were counted by experimenters blinded to treatment.
IOP was elevated by approximately 4-5 mmHg in bead-injected mice; control mice did not show increase in IOP. Each retina was examined in eight locations, based on four quadrants (ventral, dorsal, nasal, temporal), as well as distance from the optic nerve head (central: ~500 microns from optic nerve; peripheral: ~1700 microns from optic nerve). No significant differences were observed in cell densities of melanopsin-expressing RGCs across all quadrants. In RBPMS-stained retinas, there was a significant reduction in RGC densities from 1453±213 to 876±258 cells/mm^2 and from 1161±188 to 719±229 cells/mm^2 in the peripheral ventral and peripheral temporal quadrants, respectively (n=6; p<0.05). No significant differences between control and OHT were observed in overall RBPMS-stained RGC density in the central quadrants.
These findings show that although OHT can induce general RGC death in peripheral retina in as early as 5 weeks after altered IOP, all six classes of melanopsin-expressing RGCs seem to be protected from degeneration at this stage. The mechanism underlying such protection is yet to be elucidated.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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