| First Author | Gambhir D | Year | 2012 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 53 |
| Issue | 4 | Pages | 2208-17 |
| PubMed ID | 22427566 | Mgi Jnum | J:196849 |
| Mgi Id | MGI:5490010 | Doi | 10.1167/iovs.11-8447 |
| Citation | Gambhir D, et al. (2012) GPR109A as an anti-inflammatory receptor in retinal pigment epithelial cells and its relevance to diabetic retinopathy. Invest Ophthalmol Vis Sci 53(4):2208-17 |
| abstractText | PURPOSE: Retinal pigment epithelium (RPE) expresses GPR109A, a receptor for the vitamin niacin and the ketone body beta-hydroxybutyrate (beta-HB). Because diabetes results in elevated levels of beta-HB, here we studied expression of the receptor in diabetic retina. We also investigated its functional relevance in RPE. METHODS: Retinal expression of GPR109A in diabetic mice and postmortem human eyes was evaluated by quantitative PCR (qPCR). ARPE-19 cells and primary wild-type and Gpr109a(-/-) mouse RPE cells were exposed to TNF-alpha in the presence or absence of niacin or beta-HB, followed by analysis of IL-6 and Ccl2 expression via real-time qPCR and ELISA. RESULTS: GPR109A expression was increased in diabetic mouse and human retina. TNF-alpha increased the expression and secretion of IL-6 and Ccl2 in ARPE-19 cells. Niacin and beta-HB suppressed these effects, implicating GPR109A as the target responsible for mediation of the observed effects. Primary RPE cells from wild-type mice behaved similarly. In contrast, GPR109A ligands failed to suppress TNF-alpha-induced expression and secretion of IL-6 and Ccl2 in primary RPE cells from Gpr109a(-/-) mice, confirming that the observed anti-inflammatory effects were mediated specifically by Gpr109a. CONCLUSIONS: GPR109A plays an anti-inflammatory role in RPE and its expression is upregulated in diabetes. Inflammation is a key causative factor in the pathogenesis of diabetic retinopathy. We speculate that the increased expression of GPR109A and elevation of its ligand beta-HB in diabetes are mechanisms by which the tissue attempts to fight inflammation in this disease. Pharmacological activation of GPR109A may therefore have therapeutic potential in clinical management of diabetic retinopathy. |
