Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin

作者：Nakazawa Toru; Takeda Masumi; Lewis Geoffrey P; Cho Kin Sang; Jiao Jianwei; Wilhelmsson Ulrika; Fisher Steven K; Pekny Milos; Chen Dong F^*; Miller Joan W

来源：Investigative Ophthalmology & Visual Science, 2007, 48(6): 2760-2768.

DOI：10.1167/iovs.06-1398

PURPOSE. To characterize the reactions of retinal glial cells (astrocytes and Muller 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 6FAP(-/-)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.

• 出版日期2007-6