Loss of Caveolin-1 Impairs Retinal Function Due to Disturbance of Subretinal Microenvironment
Loss of Caveolin-1 Impairs Retinal Function Due to Disturbance of Subretinal Microenvironment
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DOI：
10.1074/jbc.m112.353763
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发表时间：
2012-05-11
影响因子：
4.8
通讯作者：
Elliott, Michael H.
中科院分区：
文献类型：
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作者：
Li, Xiaoman;McClellan, Mark E.;Elliott, Michael H.
小窝蛋白-1（Cav-1）是小窝膜结构域的组成部分，在几种视网膜细胞类型中表达，包括光感受器、视网膜血管内皮细胞、Muller神经胶质和视网膜色素上皮（RPE）细胞。最近的证据将Cav-1与眼部疾病联系起来，包括自身免疫性葡萄膜炎，糖尿病视网膜病变和原发性开角型青光眼，但其在正常视力中的作用在很大程度上尚未确定。在这份报告中，我们表明，在体内，通过视网膜电图和锰增强MRI测量，Cav-1的消融导致内部和外部视网膜功能降低。有些令人惊讶的是，暗电流和光敏感性在来自Cav-1敲除（KO）小鼠的单个视杆中是正常的（用抽吸电极方法记录）。虽然光感受器功能基本正常，但在体外，Cav-1 KO小鼠中RPE表达的α 1-Na+/K+-ATP酶的表观K+亲和力降低。Cav-1 KO视网膜也显示出与RPE异常紧密的粘附，这可以通过用高渗介质进行短暂处理来解决，这表明外部视网膜液体稳态的改变。总的来说，这些发现表明Cav-1消融导致的视网膜功能降低不是光感受器内在的，而是涉及受损的视网膜下和/或RPE离子/流体稳态。
Caveolin-1 (Cav-1), an integral component of caveolar membrane domains, is expressed in several retinal cell types, including photoreceptors, retinal vascular endothelial cells, Muller glia, and retinal pigment epithelium (RPE) cells. Recent evidence links Cav-1 to ocular diseases, including autoimmune uveitis, diabetic retinopathy, and primary open angle glaucoma, but its role in normal vision is largely undetermined. In this report, we show that ablation of Cav-1 results in reduced inner and outer retinal function as measured, in vivo, by electroretinography and manganese-enhanced MRI. Somewhat surprisingly, dark current and light sensitivity were normal in individual rods (recorded with suction electrode methods) from Cav-1 knock-out (KO) mice. Although photoreceptor function was largely normal, in vitro, the apparent K+ affinity of the RPE-expressed alpha 1-Na+/K+-ATPase was decreased in Cav-1 KO mice. Cav-1 KO retinas also displayed unusually tight adhesion with the RPE, which could be resolved by brief treatment with hyperosmotic medium, suggesting alterations in outer retinal fluid homeostasis. Collectively, these findings demonstrate that reduced retinal function resulting from Cav-1 ablation is not photoreceptor-intrinsic but rather involves impaired subretinal and/or RPE ion/fluid homeostasis.