Hammes H P, Brownlee M, Jonczyk A, Sutter A, Preissner K T
Third Department Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Nat Med. 1996 May;2(5):529-33. doi: 10.1038/nm0596-529.
Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor-type integrins appears to be required for the survival and maturation of newly formed but not quiescent blood vessels in several vascular beds including the retina, blockade of this downstream adhesion receptor system was investigated. In a mouse model of hypoxia-induced retinal neovascularization twice daily administration of 1 to 20 mg cyclic alpha v-integrin antagonist peptide per kilogram of body weight reduced capillary proliferation in a dose-dependent fashion--maximum 76%--without obvious side effects. A cyclic control peptide displayed no inhibitory effect on neovascularization. These findings indicate that systemic application of vitronectin receptor antagonists appears to be clinically feasible and is efficient in preventing retinal neovascularization and superior to cytokine-blocking strategies.
视网膜新生血管形成是诸如早产儿视网膜病变、增殖性糖尿病视网膜病变和老年性黄斑变性等疾病导致失明的主要原因。由于在包括视网膜在内的几个血管床中，玻璃粘连蛋白受体型整合素的结扎似乎是新形成而非静止血管存活和成熟所必需的，因此研究了对这一下游黏附受体系统的阻断作用。在缺氧诱导的视网膜新生血管形成小鼠模型中，每天两次给予每千克体重1至20毫克的环状αv整合素拮抗剂肽，以剂量依赖方式减少毛细血管增殖——最大可达76%——且无明显副作用。一种环状对照肽对新生血管形成无抑制作用。这些发现表明，玻璃粘连蛋白受体拮抗剂的全身应用在临床上似乎是可行的，并且在预防视网膜新生血管形成方面是有效的，且优于细胞因子阻断策略。
