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C. Zhang, S.K. Chiang, F. Yang, J. Shen, D. Sinha, T.T. Lam, M.O. Tso; Retinal Microglial Activation and Migration Following Photic Injury . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5122.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Microglial cells have been shown to be involved in neuronal degenerations of CNS. Activated microglial cells isolated from RCS rat retinas were shown to be injurious to photoreceptor cells in vitro. This study investigates the mechanisms of migration and activation of the retinal microglial cells and their possible injurious effects to photoreceptors in light-induced retinal degeneration. Methods: Thirty-four Balb/cJ mice from Jackson Lab were kept in cyclic light for 1 wk and dark adapted for 2d before light exposure of 3h at 3.5Klux. The animals were sacrificed at 0h, 3h, 6h, 24h, 3d, and 7d of dark recovery after light exposure. Markers for identification of retinal microglial cells included rat-anti mouse CD11b and isolectin B4. TUNEL labeling and immunohistochemistry using TNF-alpha antibody were also performed. In order to determine the chemokines involved in microglial cell migration and activation in the retina, gene array using a chemokine membrane (SuperArray) and RT-PCR were performed. Results: After intense light exposure, TUNEL positive cells started to increase in the retina from 3h and reached a peak at 24h and continued until day 7. The CD11b and isolectin positive microglial cells were seen at 6h and increased significantly at 1d and 3d in the ONL after light exposure. These cells displayed round or ameboid form at 6h and 24h and then evolved to assume a more dendritic shape at 3d. Using gene array analysis, we were able to identify a significant increase of chemokine MCP-3 (monocyte chemoattractant protein-3, Scya7). RT-PCR confirmed the dramatic increase of MCP-3 gene expression in the retinas at 3h to 24h, and decreased at 3d. TNF-alpha gene expression was also significantly increased in the retinas at 3h and 24 h and decreased at 3d after light injury. Immunohistochemistry showed increased TNF-alpha positive cells in the ONL at 24h after light exposure and some of them were co-localized with CD11b immunolabeling. Conclusion: Microglial cells were activated and migrated to the ONL after retinal light injury. MCP-3 may play an important role in the induction of microglial cell activation and migration in light-induced photoreceptor degeneration. The activated microglial cells may produce toxic cytokines, such as TNF-alpha to exaggerate photoreceptor degeneration after retinal light injury.
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