Somatostatin protects human retinal pericytes from inflammation mediated by microglia. (November 2017)

• Record Type: Journal Article
• Authors: Mazzeo, Aurora; Arroba, Ana I.; Beltramo, Elena; Valverde, Angela M.; Porta, Massimo
• Is Part Of: Experimental eye research. Volume 164(2017)
• Page Start: 46
• Page End: 54
• Publication Date: 2017-11
• Subjects: Diabetic retinopathy -- Somatostatin -- Pericyte -- Microglia -- Inflammation -- Apoptosis; CM conditioned medium -- DME diabetic macula edema -- DR diabetic retinopathy -- FasL Fas ligand -- FBS fetal bovine serum -- HRP human retinal pericytes -- LPS lipopolysaccharide -- MCP-1 monocyte chemoattractant protein-1 -- NO nitric oxide -- PDGF-B Platelet-derived Growth Factor B -- PDR proliferative diabetic retinopathy -- SST somatostatin -- TNFα Tumor Necrosis Factor-α; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2017.07.011
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Diabetic retinopathy (DR) is usually considered a microvascular disease. However, involvement of the neuroretina in the early stages of DR has recently gained major credit. Inflammatory processes, leading to glial activation and neuronal apoptosis, develop early in the retina of diabetic subjects. Pericytes constitute a link between the vascular and the neural retina, play a central role in blood–retinal barrier maintenance, and may influence neuroinflammation. Somatostatin (SST) is a potent neuroprotective factor, which is down-regulated during early DR. In this paper, we have investigated the effects of the inflammatory signals triggered by the activation of microglia on inflammation and apoptosis/survival pathways in pericytes. Microglia cells (Bv-2) were stimulated with lipopolysaccharide (LPS) and/or SST. Human retinal pericytes (HRP) were exposed to conditioned media (CM) collected from Bv-2 cells in physiological conditions and in the settings described above. A panel of inflammation, apoptosis and survival mediators was analyzed. HRP treated with LPS-CM showed a significant increase of pro-inflammatory (iNos and TNFα) and pro-apoptotic mediators (FasL, active caspase-8, tBid and Bax), and a concomitant decrease in pro-survival factors (BclxL and pAkt). 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 crosstalk between microglia and retinal pericytes, evidencing a possible defensive role of microglia in the early phases of DR. Highlights: Microglia-mediated inflammation causes release of inflammatory markers in pericytes. Inflammation induces imbalanced apoptotic/survival signaling in pericytes. Caspase-8 plays a primary and independent role. Somatostatin protects human retinal pericytes from microglia-mediated inflammation. Somatostatin could be a protective agent in early diabetic retinopathy.