Involvement of integrins alpha(v)beta(3) and alpha(v)beta(5) in ocular neovascular diseases
Involvement of integrins alpha(v)beta(3) and alpha(v)beta(5) in ocular neovascular diseases
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DOI：
10.1073/pnas.93.18.9764
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发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Cheresh, DA
中科院分区：
文献类型：
--
作者：
Friedlander, M;Theesfeld, CL;Cheresh, DA
血管生成是导致灾难性视力丧失的大多数疾病的基础。最近的证据表明整合素 α(v) beta(3) 和 alpha(v) beta(5) 与血管生成过程有关。我们检测了年龄相关性黄斑变性引起的视网膜下新生血管形成或假定的眼组织胞浆菌病综合征或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眼组织中α（v）β（3）和α（v）β（5）的表达。在患有年龄相关性黄斑变性或推测的眼组织胞浆菌病的患者的具有活动性新生血管的眼组织的血管中仅观察到α(v)β(3)，而在PDR患者的组织中的血管细胞上同时存在α(v)β(3)和α(v)β(5)。由于我们在患有 PDR 视网膜新生血管的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查了全身施用的 α(v) β(3) 和 α(v) β(5) 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神经血管的形成，但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α(v)β(3)和/或α(v)β(5)拮抗剂可能有效治疗患有与血管生成相关的致盲眼病的个体。
Angiogenesis underlies the majority of eve 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 nerv 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.