Luna J, Tobe T, Mousa S A, Reilly T M, Campochiaro P A
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Lab Invest. 1996 Oct;75(4):563-73.
Integrin alpha v beta 3 is differentially expressed in angiogenic blood vessels in skin granulation tissue, and alpha v beta 3 antagonists inhibit angiogenesis in chick chorioallantoic membranes. In this study, we investigated the role of alpha v beta 3 in retinal neovascularization. There was no detectable signal for alpha v beta 3 by immunohistochemistry in normal human retina, but neovascular tissue removed from the surface of the retina of patients with diabetic retinopathy showed intense staining for alpha v beta 3 within the endothelial cells of new blood vessels. In a murine model of oxygen-induced ischemic retinopathy, there was intense staining for alpha v beta 3 in endothelial cells participating in neovascularization but no detectable staining in normal retinal blood vessels of adult mice. Synthetic peptides that bind alpha v beta 3 and perturb alpha v beta 3-mediated adhesion in vitro inhibited retinal neovascularization in the murine model when given by intraperitoneal or periocular injections. These data suggest that alpha v beta 3 antagonists may provide a useful adjunct for the treatment of retinal neovascularization.
整合素αvβ3在皮肤肉芽组织的血管生成血管中差异表达，且αvβ3拮抗剂可抑制鸡胚绒毛尿囊膜中的血管生成。在本研究中，我们调查了αvβ3在视网膜新生血管形成中的作用。在正常人视网膜中，免疫组化未检测到αvβ3的信号，但从糖尿病视网膜病变患者视网膜表面切除的新生血管组织中，新血管内皮细胞内的αvβ3显示出强烈染色。在氧诱导的缺血性视网膜病变小鼠模型中，参与新生血管形成的内皮细胞中αvβ3有强烈染色，但成年小鼠正常视网膜血管中未检测到染色。在体外结合αvβ3并干扰αvβ3介导的黏附的合成肽，经腹腔或眼周注射给药时，可抑制小鼠模型中的视网膜新生血管形成。这些数据表明，αvβ3拮抗剂可能为视网膜新生血管形成的治疗提供有用的辅助手段。
