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FJ Malecaze, M Saint-Geniez, B Knibielher, Y Audigier; Expression of the Murine Msr/apj Receptor and its Ligand Apelin is Upregulated Inside the Vessles During Retinal Development and Oxygen-induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2423.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal neovascularization is a major cause of visual loss in a variety of ocular diseases, including retinopathy of prematurity and diabetic retinopathy.We have recently identified a new G protein-coupled receptor, msr/apj, whose transcripts are detected in the endothelium during formation of the embryonic vasculature which incited us to investigate its expression during the formation of retinal vessels. Methods: The model of retinopathy of prematurity (ROP) was procuded by exposing posnatal day-7 mice to 75% oxygen for 5 days and then returning them to room air. Expression of msr/apj and its ligand apelin was examined by in situ hybridization on flamount and sections of retina of normal and ROP mice. The retinal vascular pattern was visualized by immunochemical localization of the Bandeiraea simplicifolia isolectine B4 . Results: During the retinal vascular development,the superficial layer of vessels forms at the retinal surface extending from the optic disk towards the periphery and reaching the edge of the retina by postnatal day 10. Interestingly, msr/apj transcripts are indeed associated with the forming vessels and trace the centrifugal extension of the superficial vasculature. We also show that expression of the endogenous ligand apelin is upregulated only at the leading edge of vessel formation suggesting that preproapelin transcripts are restricted to some endothelial cells at the peripheral zone of vessel extension. We used the murine model of retinopathy of prematurity to determine the involvement of the apelin signalization on neovascularization in the retina. Flatmount in situ hybridization showed high expression of msr/apj and its ligand inside forming neovessels which decreased with neovessels regression. Although the temporal expression of the msr/apj and preproapelin genes is concomitantly up-regulated there is a clear difference in their spatial patterns of expression. As previously observed during formation of normal vasculature, apelin transcripts are also restricted to the front of the branching sprouts of extending neovessels. Sections of the neovascularized retina revealed that the expression of both receptor and ligand was intense inside neovascular tufts. Conclusion: Taken together these data revealed that variations in the expression of apelin and its receptor are tightly linked to the formation and remodeling of normal and pathologic vessels, suggesting an important role for this signaling pathway in vascular development and associated diseases.
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