Characterization of a spontaneous neovascular mouse model

Abstract

Purpose: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world affecting all age groups. Neovascularization is a hallmark of complex, polygenic diseases, such as age-related macular degeneration (AMD), which affects 1 in 3 individuals over the age of 65. The growth of abnormal blood vessels leads to debilitating vision loss and eventual blindness. The novel mouse strain neoretinal vascularization (NRV)2 mice show spontaneous early chorio-retinal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model.

Methods: The present studies adhered to ARVO’s Statement for the Use of Animals in Ophthalmic and Vision Research. The NRV2 mice were examined from postnatal Day 17 (p17) to 3months. The phenotypic changes were evaluated by fundus photography, fluorescein angiography, optical coherence tomography ( MicronIII Retinal Imaging Microscope; Phoenix). Immunohistochemical and electron microscopic analysis of retina/choroid sections was performed. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis (Amira).

Results: We found that the NRV2 mice developed multifocal retinal depigmentation in the posterior fundus. Several of these depigmented areas showed vascular leakage by fluorescein angiography. Disease progression in NRV2 mice revealed that depigmentation and vascular leakage beginning around p21, increased and peaked at p25, and persisted for more than 3 months. Histological analysis revealed disruption of the retinal pigment epithelium (RPE) and the neovascular structures in the photoreceptor cell layer and at the RPE Bruch’s interface.

Conclusions: We have further characterized a model of spontaneous angiogenesis that occurs in the NRV2 mouse strain. This non-injury model of retinal neovascularization will be useful in elucidating the molecular causes of retinal neovascular disease and in developing therapeutics.

Keywords: 412 age-related macular degeneration • 609 neovascularization