Vinores S A, Derevjanik N L, Ozaki H, Okamoto N, Campochiaro P A
The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Doc Ophthalmol. 1999;97(3-4):217-28. doi: 10.1023/a:1002136712070.
To determine the mechanism of blood-retinal barrier (BRB) dysfunction in human and experimental specimens using immunocytochemistry.
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.
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.
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.
运用免疫细胞化学方法确定人类和实验标本中血视网膜屏障（BRB）功能障碍的机制。
在临床标本以及光感受器中过表达血管内皮生长因子（VEGF）的转基因小鼠的视网膜中定位血管外白蛋白。转基因小鼠视网膜还用刀豆球蛋白B4（GSA）进行标记，GSA是一种可与内皮细胞结合的凝集素。
BRB由视网膜血管内皮（RVE）细胞与视网膜色素上皮（RPE）细胞之间紧密连接的存在以及内皮细胞内小泡的缺乏所建立。当在诸如糖尿病性视网膜病变、色素性视网膜炎或黄斑囊样水肿等人类眼部疾病中发生BRB破坏时，血管外白蛋白染色显示通过紧密连接的渗漏、内皮细胞内小泡的上调以及发生退行性改变的RVE或RPE细胞的渗透。VEGF除了诱导新生血管形成（NV）外，还促进血管渗漏。在VEGF转基因小鼠中，BRB功能障碍局限于外视网膜，即NV发生的区域。GSA与新生血管和成熟血管中RVE细胞的管腔面和管腔外表面结合，并与血管渗漏区域的内皮细胞内小泡和内皮细胞间连接结合。
BRB功能障碍可能由RVE或RPE细胞紧密连接的渗漏、跨内皮小泡运输或发生退行性改变的RVE或RPE细胞的渗透介导。GSA可能是一种有用的标志物，有助于识别开放的紧密连接和内皮细胞内小泡的增加，这表明BRB功能障碍。
