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

PURPOSE. To determine the roles of glial fibrillary acidic protein (GFAP) and vimentin in Muller 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. Muller cell morphology was different and glutamine synthetase immunoreactivity was reduced in the undisturbed GFAP(-/-) vim(-/-) retinas. After retinal detachment, Muller cells formed subretinal glial scars in the wt mice. In contrast, such scars were not observed in GFAP(-/-) vim(-/-) mice. Muller 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 Muller 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. Muller 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 Muller cell reaction to retinal detachment and participation in subretinal gliosis.