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Adenylyl Cyclase/cAMP System Involvement in the Antiangiogenic Effect of Somatostatin in the Retina. Results from Transgenic Mice

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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 whether 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 with different patterns depending on sst2 expression level. The AC VII isoform mRNA and protein resulted the most affected. Indeed, in hypoxia AC VII expression was enhanced in WT retinas and it was further increased in sst2-lacking retinas, whereas in sst2 overexpressing retinas the increase of AC VII was lower than in WT retinas. 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.

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Acknowledgments

This work was supported by the Italian Ministry of University and Research (MUR, PRIN, grant 2005052312) and the Fondazione Cassa di Risparmio di Cento. We thank G. Bertolini (University of Pisa, Italy) for assistance with mouse colonies.

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Authors and Affiliations

  1. Dipartimento di Biologia, Università di Pisa, Pisa, Italy

    Chiara Ristori & Massimo Dal Monte

  2. Dipartimento di Biologia ed Evoluzione, Università di Ferrara, Via L. Borsari, 46, 44100, Ferrara, Italy

    Maria Enrica Ferretti, Barbara Pavan, Franco Cervellati & Carla Biondi

  3. Dipartimento di Scienze Ambientali, Università della Tuscia, Viterbo, Italy

    Giovanni Casini & Elisabetta Catalani

Authors
  1. Chiara Ristori
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  2. Maria Enrica Ferretti
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  3. Barbara Pavan
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  4. Franco Cervellati
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  5. Giovanni Casini
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  6. Elisabetta Catalani
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  7. Massimo Dal Monte
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  8. Carla Biondi
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Correspondence to Carla Biondi.

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Ristori, C., Ferretti, M.E., Pavan, B. et al. Adenylyl Cyclase/cAMP System Involvement in the Antiangiogenic Effect of Somatostatin in the Retina. Results from Transgenic Mice. Neurochem Res 33, 1247–1255 (2008). https://doi.org/10.1007/s11064-007-9576-6

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  • DOI: https://doi.org/10.1007/s11064-007-9576-6

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