Friedlander M, Theesfeld C L, Sugita M, Fruttiger M, Thomas M A, Chang S, Cheresh D A
Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9764-9. doi: 10.1073/pnas.93.18.9764.
Angiogenesis underlies the majority of eye diseases that result in catastrophic loss of vision. Recent evidence has implicated the integrins alpha v beta 3 and alpha v beta 5 in the angiogenic process. We examined the expression of alpha v beta 3 and alpha v beta 5 in neovascular ocular tissue from patients with subretinal neovascularization from age-related macular degeneration or the presumed ocular histoplasmosis syndrome or retinal neovascularization from proliferative diabetic retinopathy (PDR). Only alpha v beta 3 was observed on blood vessels in ocular tissues with active neovascularization from patients with age-related macular degeneration or presumed ocular histoplasmosis, whereas both alpha v beta 3 and alpha v beta 5 were present on vascular cells in tissues from patients with PDR. Since we observed both integrins on vascular cells from tissues of patients with retinal neovascularization from PDR, we examined the effects of a systemically administered cyclic peptide antagonist of alpha v beta 3 and alpha v beta 5 on retinal angiogenesis in a murine model. This antagonist specifically blocked new blood vessel formation with no effect on established vessels. These results not only reinforce the concept that retinal and subretinal neovascular diseases are distinct pathological processes, but that antagonists of alpha v beta 3 and/or alpha v beta 5 may be effective in treating individuals with blinding eye disease associated with angiogenesis.
血管生成是大多数导致视力严重丧失的眼部疾病的基础。最近的证据表明，整合素αvβ3和αvβ5参与了血管生成过程。我们检测了年龄相关性黄斑变性或疑似眼组织胞浆菌病综合征引起的视网膜下新生血管形成患者，以及增殖性糖尿病视网膜病变（PDR）引起的视网膜新生血管形成患者的新生血管性眼组织中αvβ3和αvβ5的表达。在年龄相关性黄斑变性或疑似眼组织胞浆菌病患者有活跃新生血管形成的眼组织血管上，仅观察到αvβ3，而在PDR患者组织的血管细胞上同时存在αvβ3和αvβ5。由于我们在PDR引起的视网膜新生血管形成患者组织的血管细胞上观察到了这两种整合素，因此我们在小鼠模型中检测了一种全身给药的αvβ3和αvβ5环肽拮抗剂对视网膜血管生成的影响。这种拮抗剂特异性地阻断了新血管的形成，对已形成的血管没有影响。这些结果不仅强化了视网膜和视网膜下新生血管疾病是不同病理过程的概念，而且αvβ3和/或αvβ5拮抗剂可能有效治疗与血管生成相关的致盲性眼病患者。
