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F. Dijk, W. Kamphuis, A.A. B. Bergen; Increased GAP–43 Expression in the Post–ischemic Retina: An Indication of Plasticity of the Inner Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):162.
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© ARVO (1962-2015); The Authors (2016-present)
PURPOSE:To study whether cellular remodeling occurs in the post–ischemic rat retina. Retinal ischemia results in the loss of retinal ganglion and amacrine cells. Markers for specific subpopulations of amacrine cells show a transient decrease in mRNA levels (2h–72h), but a permanent (up to 4w) decrease in immunostaining. We hypothesized that this discrepancy could be explained by a small number of remaining cells that increase their expression/activity in order to sustain a relatively large network in the IPL. We studied whether ischemia/reperfusion is followed by a proliferation of specific cells. METHODS: A 60–minute ischemic period was administered unilaterally to the rat eye by raising the intra–ocular pressure, followed by reperfusion lasting between 2 hours and 4 weeks. For real–time quantitative PCR, total RNA was isolated from the retinas and expression levels of the following genes were assessed: growth–associated protein–43 (GAP43; major constituent of growth cones), nestin (intermediate filament protein associated with proliferation) doublecortin (marker for immature neurons), and transcription factors Pax6, Six3, Six6, and Dach 1. Immunocytochemical double labeling of cell specific markers with GAP–43 and nestin will be used to demonstrate outgrowth of specific cell types. Results: Following ischemia, an increase is observed in the transcript levels of GAP43 at 12–24h, and of nestin at 2h–1 week. Significant changes are not observed for doublecortin, Pax6, Six6, and Dach 1. Six3 showed a decrease in transcript levels from 6h onwards. Preliminary results at the protein level indicate that the appearance of GAP–43 immunostaining changes drastically from 48 hours of reperfusion onwards. Large agglomerates of immunostaining are observed in the outer IPL, and various ganglion somata show intense immunoreactivity. Moreover, bright fibers of variable length and thicknessare observed in the inner retina, running both horizontally and vertically. Conclusions: Ischemia/reperfusion results in an increase of GAP–43 and nestin, which are considered markers for regenerating axons, indicating that a form of remodeling occurs in the post–ischemic retina; further studies will be carried out to identify the cell types involved. Elucidating the appropriate factors to stimulate the remodeling process may eventually benefit patients suffering from inner retinal degeneration, like glaucoma patients.
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