Bile acid receptor could be innovative target in premature newborns' vision protection

Medical College of Georgia scientists have early evidence that targeting farnesoid-X-receptor, or FXR, a bile acid receptor could provide earlier, more impactful treatments for these babies, a process that could be expedited by the fact that the drugs they are studying already are used in people. A small fraction of premature babies develop retinopathy of prematurity, a leading cause of childhood blindness, which at its most severe can lead to formation of leaky blood vessels that further obstruct rather than improve vision and retinal detachment.

Key to normal blood vessel development are astrocytes, normally supportive star-shaped cells. But in the stressful environment that can come with premature birth, these essential astrocytes may essentially self-destruct, or apoptose, and begin to send the wrong message to endothelial cells.

Treatments today try to address the dysfunctional blood vessel growth that happens in response to perceived hypoxia in the retinas of babies. The approach they are pursuing should begin to work in the period of hyperoxia that occurs with oxygen supplementation, which is when normal blood vessel development should be happening because the baby should still be developing in the mother. The scientists suspect that that the reduced expression and signaling from FXR that happens in retinopathy of prematurity is key to the destruction that happens instead and likely enhancing its expression will help reduce or eliminate it.

They are looking at two drugs that induce FXR signaling, obeticholic acid, which is already prescribed clinically to treat a liver condition in which the bile ducts are destroyed and works to increase bile production and elimination in the liver, and chendeoxycholic acid, a natural bile acid that also is used clinically to dissolve gallstones. They are looking at the impact of the drugs on different stages of retinopathy of prematurity. They also want to further explore the normal role of FXR in the retina and how that is altered in retinopathy of prematurity using models where FXR has been knocked out of astrocytes and endothelial cells.

Reference:

MEDICAL COLLEGE OF GEORGIA AT AUGUSTA UNIVERSITY, MENAKA C. THOUNAOJAM et al.