Aim: 

The peptide somatostatin (SRIF) is a candidate for novel therapies against proliferative retinopathy. Of the five SRIF receptors (sst1-5), sst2 is the main mediator of angioinhibitory activity of SRIF. In line with our demonstration that levels of functional sst2 are critical in determining the severity of retinal neovascularization, we investigated whether a correlation exists between angiogenetic responses and sst2 expression in a mouse model of oxygen-induced retinopathy (OIR).

Methods: 

OIR was induced following established protocols (Dal Monte et al., IOVS 48, 2007). Western blot, immunohistochemistry, binding assay and real time RT-PCR were used to determine sst2 expression.

Results: 

Western blot and binding assay revealed a substantial decrease in sst2 levels in OIR. Quantitative evaluation of sst2A immunofluorescence demonstrated that sst2A decreased in retinal cells whereas it increased in retinal vessels. Consistent with the notion that sst2 decrease results in dysregulation of glutamate homeostasis, we also found an increased expression of glutamine synthetase in Muller cells. The decrease in sst2 binding and immunolabeling was not associated with variations in the rate of gene expression, indicating that the observed changes are related to post-transcriptional events.

Conclusion: 

This is the first demonstration of dynamic changes in sst2 expression in invivo models of growing vascular endothelium. The increased expression of sst2 by proliferating retinal vessels is in line with previous observations in cultured human endothelial cells.