Adenylyl cyclase/cAMP system involvement in the antiangiogenic effect of somatostatin in the retina. Results from transgenic mice.

Abstract

Neoangiogenesis is a response to retinal hypoxia that is inhibited by somatostatin (SRIF) through its subtype 2 receptor (sst2). Using a mouse model of hypoxia-induced retinopathy, we investigated the possibility that inhibition of adenylyl cyclase (AC) is involved in SRIF anti-angiogenic actions. Hypoxia increased AC responsiveness in wild type (WT) retinas and in retinas lacking sst2, but not in sst2-overexpressing retinas. Hypoxia also altered AC isoform expression, but with different patterns depending on sst2 expression level. Among the nine AC isoforms, AC VII isoform mRNA and protein resulted the most affected. Indeed, in hypoxia AC VII expression was significantly enhanced in WT retinas and it was further increased in sst2-lacking retinas, but not in retinas overexpressing sst2. These data suggest an involvement of AC/cAMP in mediating both hypoxia-evoked retinal neoangiogenesis and SRIF protective actions. The AC VII isoform is a candidate to a main role in these mechanisms.