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HA Quigley, H Levkovitch-Verbin, KR G Martin, ME Pease, LA Baumrind, DF Valenta; A Model to Study Differences Between Primary and Secondary Degeneration in Retinal Ganglion Cells in Rats by Partial Optic Nerve Transection . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2181.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To differentiate mechanisms of primary and secondary retinal ganglion cell (RGC) degeneration in a rat model of optic nerve injury. Methods:: Under general anesthesia, a modified diamond knife reproducibly transected the superior one-third of the orbital optic nerve in albino Wistar rats. RGC survival was evaluated by retrograde filling with Fluorogold dye injected into the superior colliculus one week prior to nerve injury, and the number of optic nerve axons was counted in cross-sections. Initial experiments with 56 rats counted the number of remaining RGCs in 24 regions of retinal whole mounts after transection at 4 and 8 days, 4 and 9 weeks. Five bilateral controls and five sham-operated rats were compared to transected eyes. In additional rats with similar partial transection, the prevalence of TUNEL-positive RGC was compared in superior and inferior retina and immunohistochemical labelling for activation of phospho-c-Jun and caspases 3, 8, and 9 were compared in the superior and inferior retina. Results:At 4 and 8 days after injury, superior RGCs showed 30% and 63% loss (p=0.02 and 0.001, n=8 rats/group), while sham operated eyes had no significant loss. At 8 days, inferior RGCs were 4.8% fewer than control (p =0.16). By 4 weeks, there was 46% loss superiorly and 39% loss in inferior retinal zones (both p <0.001). At 9 weeks, there was 41% loss superiorly and 35% loss inferiorly (both p < 0.01). Detailed, serial section studies of the topography of RGC axons in the optic nerve show an orderly arrangement of fibers that are segregated by cell body position in the retina, and confirmed that only the upper optic nerve had been directly injured. Results of immunohistochemical comparisons of the alterations in superior and inferior retina will be presented. Conclusion:A model of partial optic nerve transection in rats showed rapid loss of directly injured RGC in the superior retina and delayed, but significant secondary loss of RGC in the inferior retina, whose axons were not directly severed. The findings confirm similar results in monkey eyes and provide a rodent model in which pharmacological interventions against secondary degeneration can be tested.
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