R-cadherin peptide antagonists disrupt normal retina developmental vascularization. (A) When R-cadherin peptide antagonists (cyclic IDS) were injected intravitreally on postnatal day 2, formation of the superficial vasculature was greatly disrupted when compared to uninjected (normal retinas) or control (cyclic INP)—injected retinas. Each image is a montage of 5 photographs. Original magnification × 10. (B) Injection of R-cadherin blocking cyclic IDS peptides resulted in decreased vascular migration toward the retinal periphery and a reduction in the total length of retinal vessels (P < .01). These results were similar to injections of the previously characterized, nonspecific, cyclic HAV peptide. Injection of N-cadherin—specific, cyclic INP peptides resulted in relatively normal levels of retinal superficial vascularization. Error bars indicate standard deviation. (C) Injection of cyclic IDS, but not cyclic INP, peptides disrupted normal formation of the deep retinal vascular plexuses with more than a 10-fold increase in the number of extra deep vessels observed. Error bars indicate standard deviation. (D) Injection of cyclic IDS peptides at postnatal day 7, just prior to formation of the deep vascular plexus, caused vessels to migrate past the normal deep vascular plexus (arrows) and into the normally avascular photoreceptor layer. The deep vascular plexus formed normally when cyclic INP peptides were injected, demonstrating a specific role for R-cadherin during endothelial cell guidance to the 3 vascular plexuses. Original magnification × 10 (upper panels) and × 20 (lower panels).