McLeod D Scott, Lutty Gerard A
Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
Eye Brain. 2016 May 20;8:55-65. doi: 10.2147/EB.S94443. eCollection 2016.
Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR) was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF.
犬类浅表视网膜血管系统的发育与人类视网膜血管系统的发育机制相似；它们都是通过血管生成、分化以及称为成血管细胞的血管前体细胞的组装来发育的。犬类氧诱导性视网膜病变（OIR）最初由阿诺尔·帕茨开发，旨在通过实验确定高氧对视网膜血管系统发育的影响。犬类OIR模型与人类早产儿视网膜病变有许多共同特征。将1日龄幼犬暴露于高氧环境4天会导致整个视网膜血管闭塞。动物回到正常空气环境后，血管增殖旺盛。最初的小视网膜前新生血管形成相互吻合，形成大的视网膜前膜，最终导致牵引性视网膜皱褶。犬类模型的终末期病理与人类早产儿视网膜病变的IV期相似。因此，犬类OIR是评估针对VEGF及其受体的药物反应的绝佳平台。对VEGF-R2抗体和VEGF陷阱的评估表明，应降低剂量，以便抑制视网膜前新生血管形成，但视网膜再血管化能够进行，使周边视网膜血管化并防止其成为VEGF的来源。
