Cellular mechanisms of blood-retinal barrier dysfunction in macular edema
Cellular mechanisms of blood-retinal barrier dysfunction in macular edema
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DOI：
10.1023/a:1002136712070
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发表时间：
1999-01-01
影响因子：
1.4
通讯作者：
Campochiaro, PA
中科院分区：
文献类型：
--
作者：
Vinores, SA;Derevjanik, NL;Campochiaro, PA
目的：应用免疫细胞化学方法探讨血视网膜屏障（BRB）功能障碍的发生机制。方法：将血管外白蛋白定位于光感受器中过表达血管内皮生长因子（VEGF）的转基因小鼠的临床标本和视网膜中。转基因小鼠视网膜也用Griffonia simplicifolia isolectin-B4 （GSA）标记，GSA是一种结合内皮细胞的凝集素。结果：视网膜血管内皮细胞（RVE）和RPE细胞之间存在紧密连接，内皮细胞内缺乏囊泡，从而建立了BRB。当BRB在糖尿病视网膜病变、视网膜色素变性或囊样黄斑水肿等眼部疾病中发生分解时，血管外白蛋白染色显示紧密连接渗漏，内皮内小泡上调，RVE或RPE细胞浸润，发生退行性改变。VEGF除了诱导新生血管（NV）外，还促进血管渗漏。在VEGF转基因小鼠中，BRB失败局限于视网膜外，即NV发生的区域。GSA结合在新血管和已建立血管的RVE细胞的管腔和腔壁表面，以及血管渗漏区域的内皮内囊泡和内皮细胞间连接处。结论：BRB功能障碍可能是通过RVE或RPE细胞的紧密连接渗漏，通过跨内皮泡运输，或通过RVE或RPE细胞发生退行性改变的渗透介导的。GSA可能是一个有用的标志物，可以帮助识别开放的紧密连接和内皮细胞内囊泡的增加，这是BRB衰竭的指示。
Purpose: To determine the mechanism of blood-retinal barrier (BRB) dysfunction in human and experimental specimens using immunocytochemistry. Methods: Extravascular albumin was localized in clinical specimens and retinas from transgenic mice that overexpress vascular endothelial growth factor (VEGF) in the photoreceptors. Transgenic mouse retinas were also labeled with Griffonia simplicifolia isolectin-B4 (GSA), a lectin that binds to endothelial cells. Results: The BRB is established by the presence of tight junctions between the retinal vascular endothelial (RVE) cells and the RPE cells and by a paucity of intraendothelial cell vesicles. When BRB breakdown occurs in human ocular disorders such as diabetic retinopathy, retinitis pigmentosa, or cystoid macular edema, staining for extravascular albumin reveals leakage through the tight junctions, an upregulation of intraendothelial vesicles, and permeation of RVE or RPE cells that have undergone degenerative changes. VEGF, in addition to inducing neovascularization (NV), promotes vascular leakage. In VEGF transgenic mice, BRB failure is confined to the outer retina, the area where NV occurs. GSA binds to the luminal and abluminal surfaces of RVE cells in new and established vessels and to intraendothelial vesicles and interendothelial cell junctions in areas of vascular leakage. Conclusion: BRB dysfunction may be mediated by leakage through the tight junctions of RVE or RPE cells, by trans-endothelial vesicular transport, or by permeation of RVE or RPE cells that have undergone degenerative changes. GSA may be a useful marker to assist in recognizing open tight junctions and an increase in intraendothelial cell vesicles, which are indicative of BRB failure.