A Spontaneous CNV Model Provides New Tool to Understand AMD

Introduction

Numerous models have been developed to study ocular neovascularization. One of the first, laser-induced choroidal neovascularization (CNV) was originally developed in primates ¹ and later adapted to rodents. ² This model has proven to be a robust tool for evaluating potential therapies for exudative AMD. Work using the laser-induced CNV model provided the critical proof of concept that paved the way for the development of photodynamic therapy, the first approved therapy for exudative AMD and subsequently the highly effective anti-VEGF treatments currently in use today. ³ While the laser model remains a workhorse for ophthalmic drug discovery, the need to develop additional models to the probe the biological processes driving neovascularization remains. 

The report by Nagai et al. ⁴ describes spontaneous CNV (sCNV) in a mutant mouse (JR5558) that recapitulates many of the key features of the human disease. Notably, the authors convincingly demonstrated that the neovascularization arises from the choroidal vasculature. This is in contrast to many genetic mouse models where the neovascularization is retinal in origin. ² Similar to the human disease, later stages of the sCNV model are characterized by edema, local gliosis, and neuronal dysfunction. These are aspects of CNV not captured in the laser-induced model, where there is an acute thermal injury to the choriocapillaris, retinal pigmented epithelium, and photoreceptors. Additionally, as in the human disease, the authors demonstrated a role for VEGF in driving the pathology. Further, unlike other CNV models in which the lesions are self-limiting and natural regression is observed, lesions in this model persist for at least 3 months. Thus, this model should be more amenable to interventional type strategies for evaluating novel targets and treatments as well provide an additional tool to investigate the underlying mechanisms of CNV.