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Abnormal reactivity of muller cells after retinal detachment in mice deficient in GFAP and vimentin.

Journal article
Authors Mark R Verardo
Geoffrey P Lewis
Masumi Takeda
Kenneth A Linberg
Jiyun Byun
Gabriel Luna
Ulrika Wilhelmsson
Milos Pekny
Dong-Feng Chen
Steven K Fisher
Published in Investigative ophthalmology & visual science
Volume 49
Issue 8
Pages 3659-65
ISSN 1552-5783
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Pages 3659-65
Language en
Links dx.doi.org/10.1167/iovs.07-1474
Keywords Animals, Disease Models, Animal, Fluorescent Antibody Technique, Indirect, Glutamate-Ammonia Ligase, metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Confocal, Microscopy, Electron, Transmission, Nerve Tissue Proteins, physiology, Neuroglia, metabolism, pathology, Photoreceptor Cells, Vertebrate, metabolism, pathology, Retina, metabolism, pathology, Retinal Bipolar Cells, metabolism, pathology, Retinal Detachment, metabolism, pathology, Retinal Ganglion Cells, metabolism, pathology, Retinal Horizontal Cells, metabolism, pathology, Rod Opsins, metabolism, S100 Proteins, metabolism, Up-Regulation, Vimentin, physiology
Subject categories Neurobiology

Abstract

PURPOSE: To determine the roles of glial fibrillary acidic protein (GFAP) and vimentin in M?ller cell reactivity. METHODS: Retinal detachments were created in mice deficient for GFAP and vimentin (GFAP(-/-)vim(-/-)) and age-matched wild-type (wt) mice. The reactivity of the retina was studied by immunofluorescence and electron microscopy. RESULTS: M?ller cell morphology was different and glutamine synthetase immunoreactivity was reduced in the undisturbed GFAP(-/-)vim(-/-) retinas. After retinal detachment, M?ller cells formed subretinal glial scars in the wt mice. In contrast, such scars were not observed in GFAP(-/-)vim(-/-) mice. M?ller cells, which normally elongate and thicken in response to detachment, appeared compressed, thin, and "spikey" in the GFAP(-/-)vim(-/-) mice. The end foot region of M?ller cells in the GFAP(-/-)vim(-/-) mice often sheared away from the rest of the retina during detachment, corroborating earlier results showing decreased resistance of this region in GFAP(-/-)vim(-/-) retinas to mechanical stress. In regions with end foot shearing, ganglion cells showed intense neurite sprouting, as revealed by anti-neurofilament labeling, a response rarely observed in wt mice. CONCLUSIONS: M?ller cells are subtly different in the GFAP(-/-)vim(-/-) mouse retina before detachment. The end foot region of these cells may be structurally reinforced by the presence of the intermediate filament cytoskeleton, and our data suggest a critical role for these proteins in M?ller cell reaction to retinal detachment and participation in subretinal gliosis.

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