Purchase this article with an account.
Deeksha Gambhir, Sudha Ananth, Rajalakshmi Veeranan-Karmegam, Jaya P. Gnana Prakasam, Vadivel Ganapathy, Pamela M. Martin; The Anti-inflammatory Receptor GPR109A Regulates Angiopoeitin-like-4 (ANGPTL4) Expression in Retina: Potential New Link Between Regulation of Inflammatory and Angiogenic Signaling Mechanisms in Diabetic Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5777.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
GPR109A is the G-protein coupled receptor (GPCR) for niacin. ß-hydroxybutyrate, a ketone body elevated substantially in uncontrolled diabetes, is a physiologic ligand. We reported recently on expression of the receptor in retina and on the potent anti-inflammatory effects elicited upon its activation in cultured retinal cells. GPCRs are involved in a wide variety of physiological responses and activation of a single GPCR may affect multiple signaling pathways. Given the crucial roles of inflammation and unregulated angiogenesis in the pathogenesis/progression of diabetic retinopathy, here we asked whether GPR109A might influence also expression of angiopoietin-like-4 (ANGPTL4), a gene that has received much attention of late as a critical regulator of pathologic angiogenesis and vascular permeability in retina.
qPCR and immunofluorescence techniques were used to examine ANGPTL4 and/or GPR109A expression in (1) diabetic human and/or mouse retina, (2) Gpr109a+/+ and Gpr109a-/- mouse retina, and (3) primary RPE cells isolated from Gpr109a+/+ and Gpr109a-/- mouse eyes. The effect of GPR109A activation on ANGPTL4 expression was examined in ARPE-19 and primary RPE cells cultured in the presence or absence of the GPR109A-specific ligands niacin or ß-hydroxybutyrate.
Expression of GPR109A and ANGPTL4 are inversely regulated, increased expression of one is associated with decreased expression of the other. Under diabetic conditions, GPR109A is up-regulated; whereas, ANGPTL4 is down-regulated . Additionally, absence of Gpr109a (Gpr109a-/-) is associated with upregulation of ANGPTL4.
GPR109A may be involved in the regulation of ANGPTL4 in retina. This study represents the first report of a potential link between these two genes. Inflammation and pathologic angiogenesis are critically involved in diabetic retinopathy. Hence, therapies targeted at limiting these factors have tremendous potential for slowing/preventing progression of the disease. GPR109A may represent one such therapeutic target capable of modulating each of these factors. Future studies will be devoted to exploring this possibility in diabetic retina in vivo.
This PDF is available to Subscribers Only