Turning a blind eye to anti-VEGF toxicities

Abstract

Excessive blood vessel growth is a key feature of many retinal diseases, and recently, anti-VEGF therapy has been successfully applied to treat neovascular age-related macular degeneration (AMD), diabetic macular edema, and retinal vein occlusion. In this issue of the JCI, Kurihara et al. reveal an essential role of Vegfa in maintaining choroid vasculature and cone photoreceptors, critical for central and color vision. Their findings suggest that therapeutic approaches to blocking VEGF signaling in retinal diseases might have unexpected detrimental side effects and that the development of alternative strategies might be necessary.

Figure 1. Vegfa produced by RPE cells is required for maintenance of the subretinal vasculature and cone photoreceptors in mice.

(A) In the adult eye, retinal pigment epithelial cells produce Vegfa, which is required for maintenance of the fenestrated choriocapillaris. (B) Following RPE-specific deletion of the Vegfa gene from adult mice, the choriocapillaris rapidly disappears and is associated with death of cone photoreceptors required for central and color vision. In contrast, the rod photoreceptors are not damaged.