Genetic inactivation of the adenosine A 2A receptor attenuates pathologic but not developmental angiogenesis in the mouse retina

X. L. Liu Xiao-Ling, Rong Zhou, Qi Qi Pan, Xiao Lin Jia, Wei Na Gao, Jun Wu, Jing Lin, Jiang Fan Chen

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33 Scopus citations


PURPOSE. The adenosine A 2A receptor (A 2AR) modulates normal vascularization and pathologic angiogenesis in many tissues and may contribute to the pathogenesis of retinopathy of prematurity (ROP) characterized by abnormal retinal vascularization in surviving premature infants. Here, the authors studied the effects of the genetic inactivation of A 2AR on normal retinal vascularization and the development of pathologic angiogenesis in oxygen-induced retinopathy (OIR), an animal model of ROP. METHODS. After exposure to 75% oxygen for 5 days (postnatal day [P] 7-P12) and subsequently to room air for the next 9 days (P13-P21), we evaluated retinal vascular morphology by ADPase staining in retinal whole mounts, retinal neovascularization response by histochemistry in serial retinal sections, and retinal VEGF gene expression by real-time PCR analysis in A 2AR knockout (KO) mice and their wild-type (WT) littermates. RESULTS. At P17, A 2AR KO mice displayed attenuated OIR compared with WT littermates, as evidenced by reduced vasoobliteration and areas of nonperfusion in the center of the retina, reduced pathologic angiogenesis as evident by decreased non-ganglion cells and neovascular nuclei, and inhibited hypoxia-induced retinal VEGF gene expression. Notably, the attenuation of pathologic angiogenesis by A 2AR inactivation was selective for OIR because it did not affect normal retinal vascularization during postnatal development. CONCLUSIONS. These findings provide the first evidence that A 2AR is critical for the development of OIR and suggest a novel therapeutic approach of A 2AR inactivation for ROP by selectively targeting pathologic but not developmental angiogenesis in the retina.

Original languageEnglish
Pages (from-to)6625-6632
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number12
StatePublished - Dec 2010


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