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M. H. Elliott, M. E. McClellan, M. N. A. Mandal, J. D. Ash; Abnormal Adhesion of the Retina to the Retinal Pigment Epithelium in Caveolin-1 Null Mice: Possible Relationship to Edema. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3415.
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Retinal edema is a clinically relevant event in retinal disease that negatively influences cell survival and function. The osmotic environment of the outer retina is tightly regulated by transport activities in the RPE and Müller glia. Proteins involved in ion and water transport localize to caveolae, flask-shaped invaginations of the plasma membrane containing the coat protein, Cav-1. Mice null for Cav-1 have reduced retinal function as measured by electroretinography that is not detectable in recordings from isolated rods indicating that photoreceptors are healthy but that the photoreceptor microenvironment is pathological. Here, we report on an abnormality in the interaction between the retina and the RPE that may result from outer retinal edema in Cav-1 null mice.
Eyecups from Cav-1 null and control mice were prepared and incubated in either Hank’s balanced salt solution (HBSS) or HBSS containing 600 mM sucrose prior to peeling neural retinas from eyecups. Retinal adhesion to the RPE was determined by quantifying melanin pigment associated with the neural retina (Nadrot et al., 2006, Am J Physiol; Endo et al., 1988, IOVS). Gene expression was compared between Cav-1 null and control mice by microarray and qRT-PCR analyses. Immunoblot and immunohistochemical analyses of proteins involved in ionic homeostasis were also performed.
Melanin pigment content was 3.7-fold higher in Cav-1 null retinas compared to controls (34.2 ± 5.8 vs 9.3 ± 4.4 µg melanin/mg protein, respectively) in retinas peeled from eyecups incubated in HBSS. Pigment adhesion was reduced 2.6-fold when Cav-1 null retinas were incubated in HBSS containing 600 mM sucrose. Microarray, qRT-PCR, and immunoblot analyses revealed upregulation of regulators of Na/K-ATPase activity, FXYD2 and FXYD3 in Cav-1 null mice. Immunohistochemical analysis suggested that FXYD2 upregulation occurs in Muller glial cells.
Our results suggest that deletion of Cav-1 results in abnormal adhesion between the retina and RPE indicating fluid and/or ion imbalances in the photoreceptor matrix. Similar results have been observed following pharmacological inhibition of Na/K-ATPase activity by ouabain suggesting that the activity of the Na/K-ATPase is altered in retina and/or RPE from Cav-1 null mice. These results suggest that Cav-1 plays a role in maintaining ion and fluid homeostasis and preventing retinal edema.
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