Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease
Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease
复制标题
DOI：
10.1038/nm877
复制
发表时间：
2003-06-01
期刊：
影响因子：
82.9
通讯作者：
Adamis, AP
中科院分区：
文献类型：
--
作者：
Ishida, S;Yamashiro, K;Adamis, AP
视网膜缺血可引起威胁视力的病理性新生血管。然而，视网膜缺血的机制尚不完全清楚。在这里，我们已经表明白细胞在正常发育期间修剪视网膜血管，并在疾病中消除它。从正常大鼠出生后第5天（P5）开始，血管修剪从中央开始向周围延伸，留下一个密度较小、口径较小的脉管系统。这种剪枝与视网膜血管细胞间黏附分子-1 （ICAM-1）的表达相关，并与部分细胞毒性T淋巴细胞组成的黏附白细胞向外移动的波相吻合。白细胞通过CD18粘附血管，并通过Fas配体（FasL）介导的内皮细胞凋亡对其进行重构。在氧诱导的缺血性视网膜病变模型中，这个过程被夸大了。白细胞利用CD18和FasL消灭视网膜血管，留下大面积的缺血视网膜。在体外，从暴露于氧的新生儿中分离的T淋巴细胞诱导fasl介导的高氧内皮细胞凋亡。以这些通路为靶点可能有助于治疗视网膜缺血，这是导致视力丧失和失明的主要原因。
Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness.