Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies.

Kynurenine (KYN) is a metabolite of tryptophan, proposed for the treatment of corneal diseases. Our goal was to evaluate the effects of KYN on normal human corneal and conjunctival epithelial cells in vitro and the re-epithelization of corneal erosion in rabbits. In our study, we used corneal (10.014 pRSV-T) and conjunctival (HC0597) epithelium cell cultures. KYN was applied at a concentration range of 1-100 µM for 24 and 48 h. We examined the effects on cellular metabolism, viability, interleukin-1β (IL-1β), IL-6, IL-10 secretion, cytoskeleton organization and transwell migration ability. Following a bilateral corneal de-epithelialization, the rabbits received drops containing 1% KYN and a saline solution to the contralateral control eye, 5 times daily. Digital images were analyzed using the EPCO 2000 software. The metabolic activity of cells was slightly decreased by KYN in the corneal but not in the conjunctival epithelium. The viability of both epithelia was improved by KYN; it caused alterations in the secretion of IL-6 and IL-10 but not IL-1β. It had no impact on both epithelia morphology and the organization of the cellular cytoskeleton. KYN stimulated the formation of pseudopodia projections in both epithelia in vitro, which may be important in terms of wound healing. However, there were no differences in the re-epithelization rate in vivo. At the tested concentrations, KYN was not toxic for the corneal and the conjunctival epithelium in vitro and did not affect corneal re-epithelization in rabbits in vivo. Our results suggest that KYN may be taken into consideration for the treatment of ocular disorders.