PURPOSE: To determine whether the somatostatin receptor 2 (sst(2)) influences angiogenesis and its associated factors in a model of hypoxia-induced retinal neovascularization. METHODS: sst(1)-knockout (KO) mice, in which sst(2) is overexpressed and overfunctional, and sst(2)-KO mice were used. Angiogenesis was evaluated in fluorescein-perfused retinas. Angiogenesis-associated factors were determined by RT-PCR and immunohistochemistry. RESULTS: Retinal neovascularization was increased in sst(2)-KO mice, but remained unchanged in sst(1)-KO compared with wild-type (WT) mice. Retinal levels of sst(2) mRNA were not affected by hypoxia. Normoxic levels of angiogenesis regulators were similar in WT and KO retinas except for mRNA levels of IGF-1, Ang-2, and its receptor Tie-2. In WT, hypoxia induced an increase in mRNA levels of (1) VEGF and its receptors, (2) IGF-1R, and (3) Ang-2 and Tie-2. The increase in VEGF and IGF-1R mRNAs was more pronounced after sst(2) loss, but was less pronounced when sst(2) was overexpressed. In addition, in hypoxic retinas, sst(2) loss increased IGF-1 mRNA, whereas it decreased Ang-1, Tie-1, and Tie-2 mRNA levels. Moreover, Tie-1 mRNA increased when sst(2) was overexpressed. Immunohistochemistry confirmed the results in hypoxic retinas on increased expression of VEGF, IGF-1, and their receptors after sst(2) loss. It also allowed the localization of these factors to specific retinal cells. In this respect, VEGFR-2, IGF-1, and IGF-1R were localized to Müller cells. CONCLUSIONS: These results suggest that sst(2) may be protective against angiogenesis. The immediate clinical importance lies in the establishment of a potential pharmacological target based on sst(2) pharmacology.

Antiangiogenic role of somatostatin receptor 2 in a model of hypoxia-induced neovascularization in the retina: results from transgenic mice

DAL MONTE, MASSIMO;CAMMALLERI, MAURIZIO;MARTINI, DAVIDE;CASINI, GIOVANNI;BAGNOLI, PAOLA
2007

Abstract

PURPOSE: To determine whether the somatostatin receptor 2 (sst(2)) influences angiogenesis and its associated factors in a model of hypoxia-induced retinal neovascularization. METHODS: sst(1)-knockout (KO) mice, in which sst(2) is overexpressed and overfunctional, and sst(2)-KO mice were used. Angiogenesis was evaluated in fluorescein-perfused retinas. Angiogenesis-associated factors were determined by RT-PCR and immunohistochemistry. RESULTS: Retinal neovascularization was increased in sst(2)-KO mice, but remained unchanged in sst(1)-KO compared with wild-type (WT) mice. Retinal levels of sst(2) mRNA were not affected by hypoxia. Normoxic levels of angiogenesis regulators were similar in WT and KO retinas except for mRNA levels of IGF-1, Ang-2, and its receptor Tie-2. In WT, hypoxia induced an increase in mRNA levels of (1) VEGF and its receptors, (2) IGF-1R, and (3) Ang-2 and Tie-2. The increase in VEGF and IGF-1R mRNAs was more pronounced after sst(2) loss, but was less pronounced when sst(2) was overexpressed. In addition, in hypoxic retinas, sst(2) loss increased IGF-1 mRNA, whereas it decreased Ang-1, Tie-1, and Tie-2 mRNA levels. Moreover, Tie-1 mRNA increased when sst(2) was overexpressed. Immunohistochemistry confirmed the results in hypoxic retinas on increased expression of VEGF, IGF-1, and their receptors after sst(2) loss. It also allowed the localization of these factors to specific retinal cells. In this respect, VEGFR-2, IGF-1, and IGF-1R were localized to Müller cells. CONCLUSIONS: These results suggest that sst(2) may be protective against angiogenesis. The immediate clinical importance lies in the establishment of a potential pharmacological target based on sst(2) pharmacology.
DAL MONTE, Massimo; Cammalleri, Maurizio; Martini, Davide; Casini, Giovanni; Bagnoli, Paola
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/195422
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