Localization of adenosine A2a receptor in retinal development and oxygen-induced retinopathy

PURPOSE. To investigate the association of adenosine A2a receptors (A2aR) w ith retinal vasculogenesis and angiogenesis that occurs in the canine model of oxygen-induced retinopathy (OIR). METHODS. One-day-old dogs were exposed to 100% oxygen for 4 days and killed in oxygen (5 days old) and at 3, 10, 17, and 23 days after exposure to hyp eroxia. Room air control animals were killed at 1, 5, 8, 15, 22, and 28 day s of age. Immunolocalization of A2aR was performed on frozen sections. and reaction product density was quantified using microdensitometry. Cell types were identified in serial sections using antibodies against von Willebrand factor (endothelial cells) and GFAP (astrocytes), and enzyme histochemistr y for menadione-dependent alpha-glycerophosphate dehydrogenase (M-alpha-GPD H) (to label angioblasts and del eloping blood vessels). RESULTS. A2aR immunoreactivity was associated with forming blood vessels an d angioblasts in the nerve fiber layer (NFL) of peripheral retina. As devel opment progressed, vascular labeling decreased, whereas labeling of neurona l elements increased. In OIR, A2aR immunoreactivity in the NFL was reduced after exposure to hyperoxia and significantly elevated in the inner retina. throughout vascularized retina and in advance of forming vasculature in al l oxygen-treated animals returned to room air. A2aR immunoreactivity was al so prominent in fronds of intravitreal neovascularization. CONCLUSIONS. A2aR immunoreactivity was associated with developing retinal v essels. As development progressed, vascular-associated A2aR labeling decrea sed and, concomitantly, labeling of neuronal elements increased. A2aR immun oreactivity was significantly elevated :It the edge of forming vasculature in all animals returned to room air after hyperoxia and in intravitreal neo vascular formations. These results provide additional evidence fur the impo rtance of A2aR and its ligand adenosine in retinal vascular development and in the vasoproliferative stage of canine OIR.