Differential Expression of Claudins in Retinas during Normal Development and the Angiogenesis of Oxygen-Induced Retinopathy
Differential Expression of Claudins in Retinas during Normal Development and the Angiogenesis of Oxygen-Induced Retinopathy
复制标题
正常发育过程中视网膜中 Claudins 的差异表达和氧诱导性视网膜病变的血管生成
DOI：
10.1167/iovs.11-7185
复制
发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Rizzolo, Lawrence J.
中科院分区：
文献类型：
--
作者：
Luo, Yan;Xiao, Wei;Rizzolo, Lawrence J.
PURPOSE. Angiogenesis accompanies several retinal pathologies that impair the inner blood-retinal barrier. Claudins are key structural and functional proteins of the barrier. This study compared the expression of claudins during the normal angiogenesis of development with that of oxygen-induced retinopathy.METHODS. Real-time PCR was used to monitor mRNA from postnatal day 8 (P8) to P21 in normal mice and oxygen-induced retinopathy (OIR) mice. Protein expression was monitored by immunoblotting and immunofluorescence. Isolectin B4 was used to identify blood vessels and occludin was used to identify tight junctions. Neovascularization and permeability were monitored using FITC-dextran and Evans blue.RESULTS. The mRNA of claudin-1, -2, -3, -4, -5, -12, -22, and -23 was developmentally regulated, but only claudin-1, -2, and -5 were found in the tight junctions of retinal vessels. OIR induced the formation of leaky neovascular vessels. The mRNA and protein of claudin-2 and -5 were overexpressed, whereas claudin-1 and occludin were unaffected. Despite their overexpression, each claudin was distributed throughout the cell, especially in the neovascular tufts. Occludin was retained at the lateral membranes but exhibited a punctate distribution.CONCLUSIONS. Claudin-1, -2, and -5 are the most prominent claudins of the inner blood-retinal barrier. The pathologic angiogenesis induced by oxygen formed a leaky barrier due to the mislocalization of these claudins. Studies of the mechanisms that regulate the intracellular distribution of claudins may lead to new therapeutic approaches for retinal vascular disease. (Invest Ophthalmol Vis Sci. 2011;52:7556-7564) DOI:10.1167/iovs.11-7185
