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Jose Carlos Rivera, Baraa Noueihed, Sylvain Chemtob; Altered expression of G-protein coupled receptor 56 (GPR56) is associated with pathological neovascularization during oxygen-induced retinopathy.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4279.
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G-protein coupled receptor 56 (GPR56), is a member of the adhesion-class GPCRs family highly expressed in various tissues including the central nervous system. GPR56 plays a critical role in several physiological and pathological processes such as neuronal migration, immunoregulation, and angiogenesis in tumors. However, its physiological functions and mechanisms in the eye have not been elucidated. In this study, we investigated the role of GPR56 on pathological angiogenesis in the retina using the Oxygen-Induced Retinopathy (OIR) model.
Briefly, C57BL/6 neonatal mice were exposed to 75% oxygen from postnatal day (P)7 to P12, followed by room air from P12 to P17 to induce pathological neovascularization. Control mice were kept in room air. Retinal expression of GPR56, and its proposed ligands collagen 3a (Col3a) and transglutaminase-2 (TG2) as well as, the adhesion G protein-coupled receptor B1 (Adgrb1), were evaluated by qPCR at P12, P14 and P17 in OIR and control animals. GPR56 localization in the retina was evaluated by co-immunostaining with cell-specific markers in retinal cryosections.
Our findings demonstrated that GPR56 was particularly localized on Muller cells in the retina. Interestingly, GPR56 was significantly (p<0.05) downregulated during the peak of pathological neovascularization, meanwhile, its ligands Col3 (p<0.001) and TG2 (p<0.001) remained significantly augmented. Additional to these findings, we also detected a significant downregulation of the anti-angiogenic Adgrb1 (p<0.01) during pathological angiogenesis in the OIR model.
Decreased expression of GPR56 and Adgrb1 during neovascularization phase in OIR suggests that these adhesion G protein receptors could play a critical role in the progression of pathological neovascularization. Further research is needed to elucidate the functions of these receptors in OIR and develop possible drug target receptors that help to prevent the progression of neovascularization in retinal neovascular diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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