Progressive morphological and functional defects in retinas from alpha1 integrin-null mice.
Progressive morphological and functional defects in retinas from alpha1 integrin-null mice.
复制标题
α1 整合素缺失小鼠视网膜进行性形态和功能缺陷。
DOI：
10.1167/iovs.08-2011
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发表时间：
2008
影响因子：
4.4
通讯作者：
Cosgrove,Dominic
中科院分区：
文献类型：
--
作者：
Peng,You-Wei;Zallocchi,Marisa;Meehan,DanielT;Delimont,Duane;Chang,Bo;Hawes,Norman;Wang,Weimin;Cosgrove,Dominic
目的 RPE 和基底膜之间的整合素/细胞基质相互作用在视网膜维持和功能中的作用尚未得到很好的表征。在本研究中，通过比较 α1 整合素敲除小鼠与品系/年龄匹配的野生型小鼠，评估了 α1β1 整合素对 RPE 细胞稳态和视网膜健康的功能重要性。方法对视网膜和 ARPE19 细胞进行免疫定位和蛋白质印迹分析，以检测 RPE 中 α1β1 整合素的表达。通过眼底镜检查、组织学和透射电子显微镜评估视网膜病理学。通过直接计数杆状光感受器来量化进行性视网膜损伤。通过视网膜冷冻切片的免疫组织化学分析记录了光诱导的视紫红质抑制蛋白和α-转导蛋白的易位。结果 整合素 α1β1 定位于视网膜色素上皮细胞的基底部分，与 RPE 的基底层共定位。整合素α1缺失小鼠具有迟发性进行性视网膜变性，与基底膜增厚、基底突起畸形、突触畸形和眼底镜异常相关。与野生型小鼠相比，整合素α1缺失小鼠在黑暗适应动物暴露于光后表现出转导蛋白易位明显延迟。结论 总的来说，这些数据表明 RPE 中 α1β1 整合素/基底膜相互作用在基底膜代谢和光感受器转导蛋白易位中发挥重要作用。这是第一份描述支持整合素/基底膜相互作用在 RPE 中重要作用的证据的报告。此外，该报告证明了 RPE 中整合素 α1β1 功能与视网膜病理明显之前感光细胞功能分子缺陷之间的直接联系。
Purpose The role of integrin/cell matrix interactions between the RPE and the basement membrane in retinal maintenance and function is not well characterized.In this study the functional importance of α1β1 integrin for RPE cell homeostasis and retinal health was assessed by comparing α1 integrin knockout mice with strain/age matched wild type mice. Methods Immunolocalization and western blot analysis of retinas and ARPE19 cells was performed to examine expression of α1β1 integrin in the RPE. Retinal pathology was assessed by funduscopy, histology, and transmission electron microscopy. Progressive retinal damage was quantified by direct counting of rod photoreceptors. Light-induced translocation of arrestin and α-transducin was documented by immunohistochemical analysis of retinal cryosections. Results Integrin α1β1 localizes to the basal aspect of retinal pigment epithelial cells co-localizing with the basal lamina of the RPE. Integrin α1 null mice have delayed onset progressive retinal degeneration associated with thickening of the basement membrane, dysmorphology of basal processes, synaptic malformations and funduscopic abnormalities. Integrin α1-null mice display marked delay in transducin translocation compared to wild type mice following exposure to light in dark-adapted animals. Conclusions Collectively, these data suggest an essential role for α1β1 integrin/basement membrane interactions in the RPE in basement membrane metabolism and translocation of transducin in photoreceptors. This is the first report describing evidence supporting an essential role for integrin/basement membrane interaction in the RPE. Further, this report demonstrates a direct link between integrin α1β1 function in RPE and molecular defects in photoreceptor cell function before retinal pathology is apparent.