Abstract
Purpose:
Retinal neovascularization is a major cause of blindness in proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP). Currently there are limited medical treatment options for prevention of neovascularization due to PDR and ROP. This study is to investigate the potential involvement of G-protein coupled receptors (GPCRs) in neovascular angiogenesis. GPCRs are a major drug target in the pharmaceutical industry. However, their roles in retinal neovascularization are largely unknown. .
Methods:
Oxygen-induced ischemic retinopathy (OIR) was produced by maintaining C57BL/6 wild type neonatal mice in 75% oxygen from postnatal day (P)7 to P12 and room air from P12 to P17. Control mice were kept in room air. At P17, mice retinas from each group were prepared for expression array analysis using Illumina BeadChip MouseWG-6 v2.0 (Illumina Inc., San Diego, CA). Expression data was analyzed using GenePattern (Broad Institute, Boston, MA).
Results:
Eight GPCR genes were upregulated (p-value = 0.0002) and ten GPCR genes were downregulated in OIR mouse retina (p-value = 0.097). The upregulated genes are Cckbr (cholecystokinin B receptor), F2r (coagulation factor II (thrombin) receptor), Drd4 (dopamine receptor D4), Cx3cr1 (chemokine receptor 1), P2ry5 (lysophosphatidic acid receptor 6), Ccbp2 (chemokine binding protein 2), Eltd1 (EGF, latrophilin and seven transmembrane domain containing 1), and Cxcr4 (chemokine (C-X-C motif) receptor 4). The downregulated genes are Tacr3 (tachykinin receptor 3), Bai3 (brain-specific angiogenesis inhibitor 3), Lgr5 (leucine rich repeat containing G protein coupled receptor 5), P2ry14 (purinergic receptor P2Y, G-protein coupled, 14), Darc (Duffy blood group, chemokine receptor), Gpr158 (G protein-coupled receptor 158), Gpr156 (G protein-coupled receptor 156), Adra2a (adrenergic receptor, alpha 2a), Celsr2 (cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila)), and Grm6 (glutamate receptor, metabotropic 6).
Conclusions:
These findings suggest that GPCRs may play important role in neovascularization in ischemic retinopathy. It is likely that alternations of these GPCR pathways are critically involved in the initiation and progression of retinal neovascularization. Further research to modulate the function of these GPCRs in OIR is needed to elucidate possible drug target receptors for treatment of retinal neovascular diseases.
Keywords: 700 retinal neovascularization •
533 gene/expression