Short-term hypoxia downregulates epithelial cell desquamation in vivo, but does not increase Pseudomonas aeruginosa adherence to exfoliated human corneal epithelial cells

Purpose: This study evaluates the effect of hypoxic and hypercapnic stress on bacterial adherence to surface corneal epithelial cells, as well as tear LDH levels, surface cell desquamation, and corneal swelling in normal human subjects. Methods: Sixteen eyes of eight human volunteers were successively exposed to three gas mixtures (air, 100% N₂, 95% N₂-5% CO₂) through tightly fitted goggles for six hours at two-week intervals. Exfoliated epithelial cells were collected and counted using a modified corneal irrigation chamber. Bacterial binding was determined by measuring Pseudomonas aeruginosa (PA) adherence to exfoliated corneal epithelial cells. The effects of hypoxic or hypercapnic stress on the corneal surface were also assessed by tear LDH measurement, and quantification of surface epithelial cell size and epithelial and stromal thickness were determined by in vivo confocal microscopy. Results: Short-term precorneal hypoxia significantly decreased corneal epithelial cell desquamation. Both short-term hypoxia alone and combined with hypercapnia induced significant corneal stromal swelling (7 to 8%) but did not significantly enhance PA adherence to exfoliated human corneal epithelial cells. Conclusions: This study demonstrates, for the first time, that short-term precorneal hypoxia downregulates corneal epithelial cell desquamation in humans. These results also demonstrate that short-term hypoxia alone or combined with hypercapnia does not significantly increase PA adherence to exfoliated epithelial cells from the human cornea. The results reveal that either longer hypoxic exposure or other interactive factor(s), including but not limited to the mechanical effect of the contact lens itself, may be required for promotion of increased epithelial cell-PA binding following lens wear in humans.