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Makoto Taomoto, D. Scott McLeod, Carol Merges, Gerard A. Lutty; Localization of Adenosine A2a Receptor in Retinal Development and Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2000;41(1):230-243.
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purpose. To investigate the association of adenosine A2a receptors (A2aR) with
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
hyperoxia. Room air control animals were killed at 1, 5, 8, 15, 22, and
28 days 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 histochemistry for menadione-dependentα
-glycerophosphate dehydrogenase (M-α-GPDH) (to label angioblasts
and developing blood vessels).
results. A2aR immunoreactivity was associated with forming blood vessels and
angioblasts in the nerve fiber layer (NFL) of peripheral retina. As
development progressed, vascular labeling decreased, whereas labeling
of neuronal 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 all oxygen-treated animals returned to room air.
A2aR immunoreactivity was also prominent in fronds of intravitreal
conclusions. A2aR immunoreactivity was associated with developing retinal vessels.
As development progressed, vascular-associated A2aR labeling decreased
and, concomitantly, labeling of neuronal elements increased. A2aR
immunoreactivity was significantly elevated at the edge of forming
vasculature in all animals returned to room air after hyperoxia and in
intravitreal neovascular formations. These results provide additional
evidence for the importance of A2aR and its ligand adenosine in retinal
vascular development and in the vasoproliferative stage of canine
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