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Michael H. Elliott, Xiaoman Li, Mark McClellan, Masaki Tanito, Michael L. Woodruff, Gordon L. Fain, Philippe Garteiser, Rheal Towner, Bruce A. Berkowitz, Steven J. Fliesler; Loss of Caveolin-1 Impairs Retinal Function Due to a Disturbance of the Retinal Microenvironment. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2694.
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Caveolin-1 (Cav-1) is a specialized lipid raft protein involved in cellular transport and signaling that is expressed in Müller glia, retinal pigment epithelium (RPE), photoreceptors, and vascular endothelium, and has been implicated in diabetic retinopathy, autoimmune uveitis, and glaucoma. Cav-1 may be important for maintaining proper membrane transport and retinal physiology and we have tested this possibility in these experiments.
Cav-1 KO was confirmed by Western blot analysis. Retinal structure and function were examined in adult Cav-1 knockout (KO) and wildtype (WT) mice (C57Bl/6J or B6129SF2/J). Panretinal function was assessed by electroretinography (ERG); central intraretinal ion regulation and whole retinal thickness were measured in dark-adapted animals in vivo using manganese-enhanced MRI (MEMRI); single rod photoresponses were recorded by suction electrode methods. Subretinal fluid dynamics was assessed indirectly by retinal adhesion assay. Retinal histology and ultrastructure were examined by light and electron microscopy.
Cav-1 KO mice had subnormal ERG responses and decreased central intraretinal manganese uptake (particularly outer retina), indicative of reduced dark current generation, in vivo. Interestingly, single rod dark current and intensity-response relationships were not different between KO and WT rods. Rhodopsin and other phototransduction protein levels, retinal thickness, and photoreceptor ultrastructure were normal, suggesting that the observed functional deficits are not intrinsic to photoreceptors per se. Cav-1 KO retinas displayed unusually tight adhesion with the RPE that was resolved by incubation with hyperosmotic media.
Cav-1 expression is important for the maintenance of normal retinal function and the subretinal microenvironment; loss of Cav-1 results in dysregulated ion and water balance, and reduced panretinal photoresponses.
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