sorbinil and Retinopathy-of-Prematurity

We investigated sugar metabolism in lenses isolated from infants with stage-5 retinopathy of prematurity (ROP). The lenses were incubated in 13C-labeled glucose (35.5 mM) or galactose (30 mM) for 24 h at 37.5 degrees C. Six to 8 lenses were pooled for each experiment. 13C-nuclear magnetic resonance spectroscopy was then performed on perchloric acid extracts of these lenses. Active aldose metabolism was indicated by the production of lactate. However, neither sorbitol nor dulcitol was detected. On the other hand, an experimental aldose reductase inhibitor, sorbinil, caused a decrease in the hexose monophosphate shunt activity suggesting an active polyol pathway. Both polyols therefore appeared to have been metabolized further. In addition, galactose metabolism was unique in that it not only involved a galactose-->glucose epimerization, but also a direct galactose-->ribose conversion, and a production of galactose-3-phosphate. Although it is possible that the ROP lenses have adapted to oxidative stress during the postnatal high-oxygen incubation for premature infants, we believe the observed sugar metabolism is representative of the developing human lens.

Topics: Aldehyde Reductase; Carbon Isotopes; Child, Preschool; Enzyme Inhibitors; Galactose; Glucose; Humans; Imidazoles; Imidazolidines; Infant; Infant, Newborn; Lens, Crystalline; Magnetic Resonance Spectroscopy; Pentose Phosphate Pathway; Polymers; Retinopathy of Prematurity; Vitrectomy