Oxygen uptake at the ocular surface in diabetic animals is impaired in response to central corneal injury

Abstract

Poor wound healing is one of the most devastating complications in late-stage diabetic patients. The avascular cornea does not rely on circulation for its oxygen consumption, uptaking it mainly from the atmosphere. Previous studies demonstrated that oxygen uptake (O₂U) in diabetic experimental animals and patients is significantly lower than in the non-diabetic condition. Our recent experiments show that upon wounding of the central cornea the O₂U decreased across the ocular surface, followed by two increases at 6–24 h, and at 72 h, which appeared to be important for proper wound healing. It is however not known whether the two distinct O₂U increases are maintained in diabetic ocular surface in response to corneal injury. In this study, we used an optic-fiber oxygen micro-sensor to measure O₂U across the ocular surface of streptozotocin (STZ)- induced diabetic mice and age-matched control mice following injury to the central cornea. We found that the injury causes an immediate and substantial reduction of O₂U across the ocular surface. O₂U in non-diabetic corneas increases at 2–6 h post wounding (hpw), decreasing again before the second rise to peak at 72 hpw, especially at the limbus. O₂U in the diabetic cornea decreases more markedly than that of non-diabetic control. This defective diabetic O₂U persisted, precluding the two dynamic rises in O₂U, leading to a failure in recovery. Altogether, our results suggest a previously unknown mechanism of a defective O₂U response to injury in the diabetic ocular surface, which warrants further research and may lead to new therapeutic paths.