5 ' nucleotidase and adenosine during retinal vasculogenesis and oxygen-induced retinopathy

PURPOSE. 5' nucleotidase (5'N) is a major source of the vasogenic substance adenosine in most tissues. The distribution and relative levels of 5'N and adenosine were examined in neonatal dog inner retina during normal vasculo genesis and oxygen-induced retinopathy (OIR). METHODS. Animals ranging in age from 1 to 22 days of age were used in this study. Adenosine immunolocalization was performed on frozen sections with a n antibody against adenosine conjugated to laevulinic acid using a streptav idin peroxidase technique. Triplicate room air control animals at different postnatal ages and triplicate oxygen-treated animals at different time poi nts during or after hyperoxic insult were analyzed. Adenosine immunoreactiv ity (AI) and 5'N enzyme histochemical reaction product were quantified usin g microdensitometry. Adjacent sections were incubated fur von Willebrand fa ctor to label blood vessels. RESULTS. During normal vasculogenesis, hi was most prominent within the inn er retina. The peak of immunoreactivity was located at the border of vascul arized retina throughout the period of primary retinal vasculogenesis (1-15 days of age). At 22 days when vasculogenesis was complete, AI decreased wi thin the inner retina. The highest 5'N activity was localized to inner Mull er cell processes in inner retina and decreased after vasculogenesis was co mplete. In animals killed after 4 days of oxygen breathing, the vaso-oblite rative stage of OIR, AI and 5'N activity were reduced throughout the retina . During the vasoproliferative stage, XI was markedly elevated at the edge of reforming vasculature as well as throughout the more posterior inner ret ina where 5'N activity also was elevated. AI was also in intravitreal neova scularization. CONCLUSIONS. Peak adenosine levels in the inner retina correlated temporall y with active vasculogenesis. Adenosine and 5'N levels were reduced in hype roxia and then returned to above normal levels during the vasoproliferative stage of OIR.