Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity.

IF 3.1 Q1 OPHTHALMOLOGY
Eye and Brain Pub Date : 2016-05-20 eCollection Date: 2016-01-01 DOI:10.2147/EB.S94443
D Scott McLeod, Gerard A Lutty
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引用次数: 9

Abstract

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.

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靶向VEGF治疗犬氧诱导视网膜病变-人早产儿视网膜病变模型。
犬视网膜浅表血管的发育机制与人类视网膜血管的发育机制相似;它们都是通过血管发生、分化和血管前体(称为成血管细胞)的组装而形成的。犬氧诱导视网膜病变(OIR)是由Arnall Patz首先提出的,目的是通过实验确定高氧对视网膜血管系统发育的影响。犬类视网膜病变与人类早产儿视网膜病变有许多共同的特点。1天大的狗暴露于高氧环境4天会导致整个视网膜血管闭塞。在动物回到室内空气后,血管增生非常强劲。最初的小视网膜前新生血管相互吻合形成大的视网膜前膜,最终引起牵拉性视网膜褶皱。犬模型的终末期病理与人类早产儿视网膜病变IV期相似。因此,犬OIR是评估针对VEGF及其受体的药物反应的一个很好的论坛。对VEGF- r2抗体和VEGF- trap的评估表明,剂量应该降低,以抑制视网膜前的新血管形成,但视网膜的血管重建能够进行,使周围视网膜血管化,并防止其成为VEGF的来源。
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来源期刊
Eye and Brain
Eye and Brain OPHTHALMOLOGY-
CiteScore
7.90
自引率
2.30%
发文量
12
审稿时长
16 weeks
期刊介绍: Eye and Brain is an international, peer-reviewed, open access journal focusing on basic research, clinical findings, and expert reviews in the field of visual science and neuro-ophthalmology. The journal’s unique focus is the link between two well-known visual centres, the eye and the brain, with an emphasis on the importance of such connections. All aspects of clinical and especially basic research on the visual system are addressed within the journal as well as significant future directions in vision research and therapeutic measures. This unique journal focuses on neurological aspects of vision – both physiological and pathological. The scope of the journal spans from the cornea to the associational visual cortex and all the visual centers in between. Topics range from basic biological mechanisms to therapeutic treatment, from simple organisms to humans, and utilizing techniques from molecular biology to behavior. The journal especially welcomes primary research articles or review papers that make the connection between the eye and the brain. Specific areas covered in the journal include: Physiology and pathophysiology of visual centers, Eye movement disorders and strabismus, Cellular, biochemical, and molecular features of the visual system, Structural and functional organization of the eye and of the visual cortex, Metabolic demands of the visual system, Diseases and disorders with neuro-ophthalmic manifestations, Clinical and experimental neuro-ophthalmology and visual system pathologies, Epidemiological studies.
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