Protecting the developing retina in retinopathy of prematurity

Abstract

Retinopathy of prematurity (ROP) is a major ocular disorder of the pre-term neonates with unsatisfactory treatment. In ROP, uncontrolled neovascularization happens and may protrude into vitreous cavity, leading to lipid exudates and bleeding, which can impair vision severely. Both clinical and basic research supports the role of oxidative stress in ROP. Using a murine oxygeninduced retinopathy (OIR) model, the animal model for ROP, we showed that genetic deletion of aldose reductase (AR), the first enzyme in the polyol pathway that uses NAD(P)H as a cofactor for glucose metabolism, is beneficial in protecting the neonatal retina in OIR. AR-deficient retinae displayed smaller central retinal vaso-obliterated area, less neovascularization and reduced blood vessel leakage after OIR. The attenuated amplitudes and delayed implicit time of a-wave, b-wave and oscillatory potentials recorded in electroretinogram were recovered in these retinae. There were also less morphological change in horizontal, rod bipolar and amacrine cells. Taken together, AR deficiency reduced retinal vascular changes and preserved retinal neuronal function in the mouse model of OIR, suggesting a therapeutic potential of AR inhibition in ROP treatment with beneficial effects on both retinal vessels and neurons.