Antiangiogenic role of somatostatin receptor 2 in a model of hypoxia-induced neovascularization in the retina: Results from transgenic mice
Author(s)
Dal Monte, Massimo
Cammalleri, Maurizio
Martini, Davide
Casini, Giovanni
Bagnoli, Paola
Date Issued
2007
Type
Article
Abstract
PURPOSE. To determine whether the somatostatin receptor 2 (sst2) influences angiogenesis and its associated factors in a model of hypoxia-induced retinal neovascularization.
METHODS. sst1-knockout (KO) mice, in which sst2 is overexpressed and overfunctional, and sst2-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 sst2-KO mice, but remained unchanged in sst1-KO compared with wild-type (WT) mice. Retinal levels of sst2 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 sst2 loss, but was less pronounced when sst2 was overexpressed. In addition, in hypoxic retinas, sst2 loss increased IGF-1 mRNA, whereas it decreased Ang-1, Tie-1, and Tie-2 mRNA levels. Moreover, Tie-1 mRNA increased when sst2 was overexpressed. Immunohistochemistry confirmed the results in hypoxic retinas on increased expression of VEGF, IGF-1, and their receptors after sst2 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 Mu¨ller cells.
CONCLUSIONS. These results suggest that sst2 may be protective against angiogenesis. The immediate clinical importance lies in the establishment of a potential pharmacological target based on sst2 pharmacology.
Additional information
L'articolo è disponibile sul sito dell'editore http://www.arvo.org/eweb/StartPage.aspx?Site=arvo2
Citation
Dal Monte, M. et al. 2007. Antiangiogenic role of somatostatin receptor 2 in a model of hypoxia-induced neovascularization in the retina: Results from transgenic mice. "Investigative Ophthalmology and Visual Science" 48(8):3480-3489
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