Action at a distance in the hyperoxic eye

Exposing newborns to high levels of oxygen, as occurs during the care of premature infants, can have several unfortunate effects on vessel development in the eye, including the loss of vessels within the retina and prolific growth of leaky vessels in the (normally avascular) vitreous body of the eye.

This latter effect, which can lead to retinal detachment and blindness, occurs only after the infant is returned to normoxic conditions. Intravitreal neovascularization is puzzling because it occurs at a considerable distance from the retina, where the angiogenic factor VEGF is produced.

Based on their experiments with mice deficient in the inducible nitric oxide synthase (iNOS) gene, Sennlaub and colleagues suggest a novel mechanism to explain this pattern of growth. In wild-type animals, iNOS is induced shortly after normal oxygen levels are restored, and it appears to block the formation of vessels in the retina by its effects on VEGF receptor function in neighboring cells.

In the absence of iNOS, retinal revascularization is improved, preventing the development of hypoxic conditions that drive the aberrant vascular formation in the vitreous body. Blocking iNOS activity with a specific inhibitor has a similar beneficial effect, suggesting an additional target for therapies to block the retinopathy of prematurity.