The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-10

AUTHORS

Przemyslaw Sapieha, Mirna Sirinyan, David Hamel, Karine Zaniolo, Jean-Sébastien Joyal, Jang-Hyeon Cho, Jean-Claude Honoré, Elsa Kermorvant-Duchemin, Daya R Varma, Sophie Tremblay, Martin Leduc, Lenka Rihakova, Pierre Hardy, William H Klein, Xiuqian Mu, Orval Mamer, Pierre Lachapelle, Adriana Di Polo, Christian Beauséjour, Gregor Andelfinger, Grant Mitchell, Florian Sennlaub, Sylvain Chemtob

ABSTRACT

Vascularization is essential for tissue development and in restoration of tissue integrity after an ischemic injury. In studies of vascularization, the focus has largely been placed on vascular endothelial growth factor (VEGF), yet other factors may also orchestrate this process. Here we show that succinate accumulates in the hypoxic retina of rodents and, via its cognate receptor G protein-coupled receptor-91 (GPR91), is a potent mediator of vessel growth in the settings of both normal retinal development and proliferative ischemic retinopathy. The effects of GPR91 are mediated by retinal ganglion neurons (RGCs), which, in response to increased succinate levels, regulate the production of numerous angiogenic factors including VEGF. Accordingly, succinate did not have proangiogenic effects in RGC-deficient rats. Our observations show a pathway of metabolite signaling where succinate, acting through GPR91, governs retinal angiogenesis and show the propensity of RGCs to act as sensors of ischemic stress. These findings provide a new therapeutic target for modulating revascularization. More... »

PAGES

1067-1076

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.1873

DOI

http://dx.doi.org/10.1038/nm.1873

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1005736593

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18836459


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