Oxygen uptake in human donor corneas: the centripetal gradient and its changes in culture and correlation with wounds and aminophylline treatment

Abstract

Oxygen is a diatomic element abundant in the atmosphere and is essential for homeostatic and metabolic processes within the cornea. The avascular cornea uptakes oxygen from the atmosphere and performs refractory and protective functions that are essential for eyesight. However, the spatial-temporal profile of oxygen uptake (O2U) in human corneas remains uncharacterized in literature. Utilizing the micro optrode technique and donor corneas, we demonstrated that the limbus has a significantly higher O2U than the cornea center, exhibiting a pattern of centripetal gradient of O2U. This pattern is thus conserved in the corneas of mice, rats, non-human primates, and humans, representing a metabolic feature of physiological significance, which may have diagnostic and prognostic value. Being cultured at 37{degrees}C and 5% CO2, this centripetal pattern became more prominent in the first three days, and less so on day 4. The pattern remained in the corneas with injury, increased O2U appears to correlate with wound healing, similar to patterns observed in animal models with a dynamic increase of metabolism in the periphery, followed by the limbus, and subsequent return to baseline. Administration of the drug aminophylline prevented a decrease of O2U at day 4. We conclude that the centripetal pattern of O2U is conserved across species and in the human cornea. Combined, our results suggest the functional and clinical significance of the mesoscopic metabolism pattern for further study and the use of aminophylline as a therapeutic agent to increase O2U and enhance corneal wound healing.