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K.-S. Cho, X. Wei, D. F. Chen; Potential Involvement of Monocyte in Retinal Ganglion Cell Loss in a Mouse Model of Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6395.
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Glaucoma is one of the retinal degenerative diseases leading to impairment of vision. Induction of inflammation in glaucomatous retina has been suggested to contribute to retinal ganglion cell (RGC) death. In this study, we set out to examine the role of monocytes in IOP elevation and RGC death in a mouse model of ocular hypertension.
Chronic ocular hypertension was induced unilaterally in the right eye of adult C57BL6J mice by anterior chamber injection of polystyrene microbeads (2 µl, 10 µm in diameter). The mouse IOP was assessed by a TonoLab every other day until sacrificed. Mice were killed on day 3, 5, 7, 10 and 14 post-injection of microbeads. Both eyeballs were removed and post-fixed in 4% paraformaldehyde, cryoprotected with 30% sucrose, and sectioned. Quantification of RGC death was determined with immunohistochemistry by incubating retinal sections with rabbit anti-beta-III tubulin antibody (an RGC specific marker), followed by a FITC-conjugated anti-rabbit IgG. Beta-III tubulin positive cells were counted, and the percentage of cell loss was calculated. Infiltration of monocytes in the hypertensive eye was assessed in retinal sections by immunofluorescence labeling with mouse anti-CD11b antibody. Densities of cd11b-positive cells in the retina were calculated.
The normal mouse eye exhibited an IOP of 10 +/- 1.5 mmHg. Injection of microbread induced transient elevation of IOP for approximately 4 weeks that reached a peak level of 27.2 +/- 2.7 mmHg. The fastest rate of RGC death (9.5 +/- 1.1 %) occurred between days 5 and 7 post-injection, coinciding with the peak period of monocyte infiltration as revealed by CD11b immunolabeling.
Elevation of IOP induced RGC loss and monocyte activation/infiltration into the retina, both of which were peaked around day 7 of ocular hypertension. The data suggests that infiltration of monocytes into the retina may contribute to RGC death during the early phase of ocular hypertension in glaucoma.
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