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Acta Physiologica 2008; Volume 194, Supplement 665
The 59th National Congress of the Italian Physiological Society
9/17/2008-9/19/2008
Cagliari, Italy
THE SOMATOSTATIN ANALOGUE OCTREOTIDE COUNTERACTS NEOVASCULARIZATION IN A MOUSE MODEL OF OXYGEN-INDUCED RETINOPATHY
Abstract number: P46
DAL MONTE1 M, CAMMALLERI1 M, CASINI2 G, BAGNOLI1 P
1Dept. of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy
2Dept. of Environmental Sciences, University of Tuscia, Viterbo, [email protected]
Aim:
Somatostatin (SRIF) is a well-known retinal peptide which plays an important antiangiogenic role through the activation of its receptor sst2. We tested the assumption that injection of a long acting SRIF analog with high affinity at sst2, octreotide (20 mg/kg/dose, administered subcutaneously), could reduce the severity of oxygen-induced retinopathy (OIR).
Methods:
OIR was induced in mouse retinas following established protocols (Dal Monte et al., IOVS 48, 2007). Fluorescein-conjugated dextran angiography of retinal vasculature was performed to score features of retinopathy using the Modified Retinopathy Scoring System. Western blot, ELISA and immunohistochemistry were used to evaluate angogenesis markers (VEGF, occludin, CD31).
Results:
We found that octreotide administration counteracts OIR-induced neovascularization and inhibits angiogenesis-associated markers. These observations indicate that octreotide exerts antiangiogenic actions through direct inhibitory effects on endothelial cells and/or regulating retinal levels of angiogenic factors. The further finding that the combined administration of the sst2 antagonist D-Tyr8 CYN 154806 prevents the effects of octreotide and that octreotide is without effect in sst2 KO mice further supports the possibility that sst2 activation may be protective against retinal angiogenesis.
Conclusion:
We conclude that SRIF analogues remain an important nondestructive therapeutic alternative to patients with proliferative diabetic retinopathy who have failed to respond to panretinal photocoagulation.
To cite this abstract, please use the following information:
Acta Physiologica 2008; Volume 194, Supplement 665 :P46