The succinate receptor GPR91 in neurons plays major role in retinal angiogenesis: Findings provide a new therapeutic target for modulating revascularization

In the advance online edition of Nature Medicine investigators show that the accumulation of succinate in the hypoxic retina of rodents is a potent mediator of vessel growth via GPR91.  Effects of the receptor are mediated by retinal ganglion neurons which, in response to higher succinate levels, regulate a number of angiogenic factors including VEGF (vascular endothelial growth factor).  The observations show a pathway of signaling were succinate, acting through GPR91, governs retinal angiogenesis.

Scientists from Sainte-Justine Hospital Research Center, the Université de Montréal and the Institut national de la santé et de la rechercher médicale(INSERM) in France report provide results that imply biological functions for succinate beyond energy production.  Of therapeutic importance is that these findings have implications for halting blinding diseases such as retinopathy of prematurity in infants, diabetic retinopathy in adults or age-related macular degeneration in seniors.   There are also implications related to stopping tumor growth by interfering with the GPR91 receptor and preserving neurons after trauma by activating the GPR91 receptor to help salvage neurons in damaged brain tissue following stroke or head injuries.

The reported studies took place in animals, however GPR91 is also found in humans.  An October 7, 2008 Science Daily article reports that the research could be extended to human clinical investigations in three to four years.