Nakahara Tsutomu, Hoshino Maya, Hoshino Shin-Ichiro, Mori Asami, Sakamoto Kenji, Ishii Kunio
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Exp Eye Res. 2015 Jun;135:134-45. doi: 10.1016/j.exer.2015.02.020. Epub 2015 Feb 26.
Recent studies have shown retinal blood vessel damage in experimental models of retinal degeneration. The present study aimed to provide a detailed description of the structural and functional changes in retinal vasculature induced by retinal ischemia-reperfusion (I/R) in rats. Retinal ischemia was induced for 60 min by raising the intraocular pressure to 130 mmHg. Morphological changes in vascular components (endothelial cells, pericytes, and basement membranes), the patency and perfusion of blood vessels, and expression of vascular endothelial growth factor (VEGF) were assessed in the retinas at 2, 7, and 14 days after I/R. Significant reductions in vascular densities were observed at 7 and 14 days after I/R. Pericyte loss occurred after the appearance of endothelial cell degeneration, whereas the vascular basement membranes remained unchanged. Some vessels showed no perfusion in damaged retina. A decrease in the immunoreactivity of VEGF in the region extending from the ganglion cell layer to the outer plexiform layer was evident 2 days after I/R. In retinal I/R model, retinal ganglion cells are rapidly (<2 day) damaged following reperfusion, therefore, the current results suggest that neuronal cell damage precedes capillary degeneration, and neuronal cells may play an important role in maintaining vascular structure and function through the production and release of endothelial cell survival factors, including VEGF. Neuronal cell damage could be an additional cause of progression of ischemic retinal damage by reducing blood supply to the retinal neurons due to the destruction of the blood vessel network.
近期研究表明，在视网膜变性的实验模型中存在视网膜血管损伤。本研究旨在详细描述大鼠视网膜缺血再灌注（I/R）诱导的视网膜脉管系统的结构和功能变化。通过将眼压升高至130 mmHg诱导视网膜缺血60分钟。在I/R后第2、7和14天评估视网膜中血管成分（内皮细胞、周细胞和基底膜）的形态变化、血管的通畅性和灌注以及血管内皮生长因子（VEGF）的表达。I/R后第7天和第14天观察到血管密度显著降低。周细胞丢失发生在内皮细胞变性之后，而血管基底膜保持不变。在受损视网膜中，一些血管无灌注。I/R后2天，从神经节细胞层到外丛状层区域的VEGF免疫反应性明显降低。在视网膜I/R模型中，视网膜神经节细胞在再灌注后迅速（<2天）受损，因此，目前的结果表明神经元细胞损伤先于毛细血管变性，并且神经元细胞可能通过产生和释放包括VEGF在内的内皮细胞存活因子在维持血管结构和功能中发挥重要作用。由于血管网络的破坏，神经元细胞损伤可能通过减少视网膜神经元的血液供应而成为缺血性视网膜损伤进展的另一个原因。
