TY - JOUR
T1 - The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis
AU - Sapieha, Przemyslaw
AU - Sirinyan, Mirna
AU - Hamel, David
AU - Zaniolo, Karine
AU - Joyal, Jean Sébastien
AU - Cho, Jang Hyeon
AU - Honoré, Jean Claude
AU - Kermorvant-Duchemin, Elsa
AU - Varma, Daya R.
AU - Tremblay, Sophie
AU - Leduc, Martin
AU - Rihakova, Lenka
AU - Hardy, Pierre
AU - Klein, William H.
AU - Mu, Xiuqian
AU - Mamer, Orval
AU - Lachapelle, Pierre
AU - Di Polo, Adriana
AU - Beauséjour, Christian
AU - Andelfinger, Gregor
AU - Mitchell, Grant
AU - Sennlaub, Florian
AU - Chemtob, Sylvain
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/53549118277
U2 - 10.1038/nm.1873
DO - 10.1038/nm.1873
M3 - Article
C2 - 18836459
AN - SCOPUS:53549118277
SN - 1078-8956
VL - 14
SP - 1067
EP - 1076
JO - Nature Medicine
JF - Nature Medicine
IS - 10
ER -