Somatostatin protects human retinal pericytes from microglia-mediated inflammation

Diabetic retinopathy (DR) has long been considered a microvascular disease. However, involvement of the neuronal part of the retina in the early stages of DR has recently gained major credit. Inflammatory processes, leading to glial activation and neuronal apoptosis have been shown to develop early in the retina of diabetic subjects. Somatostatin (SST) is a potent neuroprotective factor synthesized in the retina and down-regulation of SST was shown during early DR. Previous work in our laboratory had demonstrated that SST has no direct effects on glucose-induced damage in human retinal pericytes (HRP). The aims of this work were to investigate the effects of inflammation mediated by the microglia on apoptosis/survival pathways in HRP and evaluate if SST could exert a protective function. We stimulated microglia cells (BV2) with lypopolysaccharide (LPS), as an inflammatory stimulus, and/or SST. HRP were subsequently exposed for 4 days to conditioned media (CM) collected by BV-2 cells in physiological conditions (ctrl) and in the above described settings. iNos and TNFα, markers of inflammation, and a panel of apoptotic/ survival mediators were analyzed by either RT-PCR or Western blotting. HRP treated with LPS-CM showed a significant increase of iNos and TNFα (+69% and +60 vs ctrl, respectively, p<0.001), while the addition of SST to LPS reverted this effect. We observed increased FasL (+85%), cleaved Caspase 8 (+110%), tBid (57%) and Bax (+10%) (pro-apoptotic markers) and decreased expression of BclxL (-70%), pAkt (-50%) (survival markers) in HRP treated with LPS-CM (p<0.05 vs ctrl). SST added to LPS was able to counteract these effects in all conditions. In conclusion, SST is able to modulate apoptosis/survival pathways in HRP during microglia-mediated inflammation. These results demonstrate a sort of crosstalk between microglia and retinal pericytes, evidencing a possible defensive role of microglia in the early phases of DR.