Retinal functional alterations in mice lacking intermediate filament proteins glial fibrillary acidic protein and vimentin

摘要

Vimentin (Vim) and glial fibrillary acidic protein (GFAP) are important components of the intermediate filament (IF) (or nanofilament) system of astroglial cells. We conducted full-field electroretinogram (ERG) recordings and found that whereas photoreceptor responses (a-wave) were normal in uninjured GFAP(-/-)Vim(-/-) mice, b-wave amplitudes were increased. Moreover, we found that Kir (inward rectifier K+) channel protein expression was reduced in the retinas of GFAP(-/-)Vim(-/-) mice and that Kir-mediated current amplitudes were lower in Muller glial cells isolated from these mice. Studies have shown that the IF system, in addition, is involved in the retinal response to injury and that attenuated Muller cell reactivity and reduced photoreceptor cell loss are observed in IF-deficient mice after experimental retinal detachment. We investigated whether the lack of IF proteins would affect cell survival in a retinal ischemia-reperfusion model. We found that although cell loss was induced in both genotypes, the number of surviving cells in the inner retina was lower in IF-deficient mice. Our findings thus show that the inability to produce GFAP and Vim affects normal retinal physiology and that the effect of IF deficiency on retinal cell survival differs, depending on the underlying pathologic condition.