Adenosine receptor antagonists and retinal neovascularization in vivo

Robert P. Mino, Polyxenie E. Spoerri, Sergio Caballero, Denifleld Player, Luiz Belardinelli, Italo Biaggioni, Maria B. Grant

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

PURPOSE. The role of adenosine receptor (AdoR) antagonists in human retinal endothelial cell function in vitro has previously been determined. In this study, efficacy of AdoR antagonist administration in reducing retinal neovascularization was examined in a mouse pup model of oxygen-induced retinopathy. METHODS. A previously described model of oxygen-induced retinal neovascularization in newborn mouse pups was used to examine the effect of various AdoR antagonists on neovascularization. The nonselective AdoR antagonist xanthine amine congener (XAC), the A 2A-selective antagonist ZM241385, the A 2B-selective antagonists 3-N-propylxanthine (enprofylline) and 3-isobutyl-8-pyrrolidinoxanthine (IPDX), and the A 1-selective antagonist cyclopentyl-1,3-dipropylxanthine (CPX) were used. After the hyperoxia exposure the animals received daily intraperitoneal injections of pharmacologically relevant doses of AdoR antagonists for 5 days. Control animals received vehicle (0.1% dimethyl sulfoxide [DMSO]) alone. The animals were then killed and perfused with fluorescein-dextran. Whole-mounts of retinas from one eye were prepared and examined, whereas the retinas of the contralateral eye were embedded, sectioned, and stained for counting neovascular nuclei extending beyond the internal limiting membrane into the vitreous. RESULTS. Angiography of wholemount retinas showed reduction of neovascular tufts in animals treated with selective A 2B AdoR antagonists. Quantification of the extraretinal neovascular nuclei showed that only animals treated with XAC, enprofylline, or IPDX showed a significant reduction in retinal neovascularization. By contrast, neither CPX nor ZM241385 had an effect on neovascularization. CONCLUSIONS. The A 2B-seIective AdoR antagonists inhibited oxygen-induced retinal neovascularization in vivo and may provide a basic for developing pharmacologic therapies for the treatment of proliferative retinonathies.

Original languageEnglish (US)
Pages (from-to)3320-3324
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number13
StatePublished - Dec 1 2001

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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  • Cite this

    Mino, R. P., Spoerri, P. E., Caballero, S., Player, D., Belardinelli, L., Biaggioni, I., & Grant, M. B. (2001). Adenosine receptor antagonists and retinal neovascularization in vivo. Investigative Ophthalmology and Visual Science, 42(13), 3320-3324.