Abnormal Reactivity of Mueller Cells After Retinal Detachment in Mice Deficient in GFAP and Vimentin
Mark Verardo 1*,
Geoffrey P. Lewis 1,
Masumi Takeda 2,
Kenneth A. Linberg 3,
Jiyun Byun 4,
Gabriel Luna 4,
Ulrika Wilhelmsson 5,
Milos Pekny 5,
Dong-Feng Chen 6,
and
Steven K. Fisher 7
1 Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California, United States; Center for Bio-Image Informatics, University of California Santa Barbara, Santa Barbara, California, United States
2 Asahikawa Medical College, Dept. of Ophthalmology, Asahikawa, Japan
3 Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California, United States
4 Center for Bio-Image Informatics, University of California Santa Barbara, Santa Barbara, California, United States
5 Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska, Academy at Goteborg University, Goteborg, Sweden
6 Schepens Eye Research Institute, Dept. of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
7 Neuroscience Research Institute, University of California, Santa Barbara, Molecular Cellular & Develop. Biology, Santa Barbara, California, 93106-5060, United States; Center for Bio-Image Informatics, University of California Santa Barbara, Santa Barbara, California, United States; Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States
* To whom correspondence should be addressed. E-mail: mark.vera{at}sbcglobal.net.
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Abstract |
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Purpose. To determine the roles of glial fibrillary acidic protein (GFAP) and vimentin in Mueller 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. Mueller cell morphology was different and glutamine synthetase immunoreactivity was reduced in the undisturbed GFAP-/-vim-/- retinas. Following retinal detachment, Mueller cells formed subretinal glial scars in the wt mice. In contrast, such scars were not observed in GFAP-/-vim-/- mice. Mueller cells which normally elongate and thicken in response to detachment appeared compressed, thin and "spikey" in the GFAP-/-vim-/- mice. The endfoot region of Mueller 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. Mueller cells are subtly different in the GFAP-/-vim-/- mouse retina before detachment. The endfoot 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 the Mueller cell's reaction to retinal detachment and participation in subretinal gliosis.
Key Words:
Mueller cell, retinal detachment, cytoskeleton
