细胞外基质相关分子在眼底新生血管形成中的作用

眼底新生血管形成是导致增生型糖尿病视网膜病变(PDR)、早产儿视网膜病变(ROP)及年龄相关性黄斑变性( AMD)患者视力丧失的主要原因之一.细胞外基质(ECM)固有成分中的胶原蛋白、弹性蛋白等经酶解后在体外研究及动物实验中已证实可促进脉络膜新生血管(CNV)、视网膜新生血管形成的发生.ECM黏附分子中的整合素α5β1与纤连蛋白在体外可促进内皮细胞黏附、增生,其抑制剂于体内则可抑制CNV、视网膜新生血管的发生,整合素αV β3及αV β5的抑制剂在体内也可发挥类似作用.黏附分子中的选择素及细胞间黏附分子则主要通过介导白细胞与内皮细胞间的相互作用促进新生血管形成.ECM降解相关的丝氨酸蛋白酶,尤其是尿激酶型纤溶酶原激活剂( uPA)(通过促进纤溶酶的生成)、基质金属蛋白酶(MMPs)(主要是MMP-2及MMP-9),在体外及体内实验中已证明可促进CNV、视网膜新生血管的发生,而I型纤溶酶原激活剂抑制剂(PAI-1)及组织金属蛋白酶抑制剂(TIMPs)则可抑制新生血管形成.对ECM相关分子在CNV、视网膜新生血管形成中作用的深入研究将为预防和治疗眼底新生血管形成提供新的思路和方法.

Extracellular matrix-related molecule on fundus neovascularization

Neovascularization is the main cause of the vision loss of the patients sufferring from proliferative diabetic retinopathy,retinopathy of prematurity and age-related macular degeneration. It is proved that collagen and elastin in the extracellular matrix contribute to the choroidal and retinal neovascularization in vitro and in vivo. Among the extracellular matrix-related adhesion molecules,integrin α5β1 could enhance the cell adhesion and hyperplasy, while its inhibitors could restrain the choroidal and retinal neovascularization in vivo, so are the inhibitors of the integrin αVβ3 and αVβ5 Selectins and intercellular adhesion molecule-1 mainly affect the neovascularization as the medium between the endothelial cells and the leucocytes. It is demonstrated that the extracellular matrix degradation- related serine proteinases （mainly urokinase-type plasminogen activator ） /matrix metalloproteinases （mainly MMP-2 and MMP-9）also could induce the choroidal and retinal neovascularization in vitro and in vivo. Furthermore, type-1 plasminogen activator inhibitor and tissue inhibitor of metalloproteinase could prevent that and the further study of the extracellular matrix-related molecules would bring out new insights and methods for the precaution and treatement of the ocular neovaseularization.