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

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.