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Toru Nakazawa, Masumi Takeda, Geoffrey P. Lewis, Kin-Sang Cho, Jianwei Jiao, Ulrika Wilhelmsson, Steven K. Fisher, Milos Pekny, Dong F. Chen, Joan W. Miller; Attenuated Glial Reactions and Photoreceptor Degeneration after Retinal Detachment in Mice Deficient in Glial Fibrillary Acidic Protein and Vimentin. Invest. Ophthalmol. Vis. Sci. 2007;48(6):2760-2768. doi: 10.1167/iovs.06-1398.
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purpose. To characterize the reactions of retinal glial cells (astrocytes and Müller cells) to retinal injury in mice that lack glial fibrillary acidic protein (GFAP) and vimentin (GFAP −/− Vim −/−) and to determine the role of glial cells in retinal detachment (RD)–induced photoreceptor degeneration.
methods. RD was induced by subretinal injection of sodium hyaluronate in adult wild-type (WT) and GFAP −/− Vim −/− mice. Astroglial reaction and subsequent monocyte recruitment were quantified by measuring extracellular signal-regulated kinase (Erk) and c-fos activation and the level of expression of chemokine monocyte chemoattractant protein (MCP)-1 and by counting monocytes/microglia in the detached retinas. Immunohistochemistry, immunoblotting, real-time quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used. RD-induced photoreceptor degeneration was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and measurement of outer nuclear layer (ONL) thickness.
results. RD-induced reactive gliosis, characterized by GFAP and vimentin upregulation, Erk and c-fos activation, MCP-1 induction, and increased monocyte recruitment in WT mice. Absence of GFAP and vimentin effectively attenuated reactive responses of retinal glial cells and monocyte infiltration. As a result, detached retinas of GFAP −/− Vim −/− mice exhibited significantly reduced numbers of TUNEL-positive photoreceptor cells and increased ONL thickness compared with those of WT mice.
conclusions. The absence of GFAP and vimentin attenuates RD-induced reactive gliosis and, subsequently, limits photoreceptor degeneration. Results of this study indicate that reactive retinal glial cells contribute critically to retinal damage induced by RD and provide a new avenue for limiting photoreceptor degeneration associated with RD and other retinal diseases or damage.
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