Kynurenic Acid Accelerates Healing of Corneal Epithelium In Vitro and In Vivo

Anna Matysik-Woźniak,Monika Turska,Waldemar A Turski,Mirosław Łańcut,Mirosław Czuczwar,Robert Rejdak,Roman Paduch,Paweł Piwowarczyk

doi:10.3390/ph14080753

Abstract

Kynurenic acid (KYNA) is an endogenous compound with a multidirectional effect. It possesses antiapoptotic, anti-inflammatory, and antioxidative properties that may be beneficial in the treatment of corneal injuries. Moreover, KYNA has been used successfully to improve the healing outcome of skin wounds. The aim of the present study is to evaluate the effects of KYNA on corneal and conjunctival cells in vitro and the re-epithelization of corneal erosion in rabbits in vivo. Normal human corneal epithelial cell (10.014 pRSV-T) and conjunctival epithelial cell (HC0597) lines were used. Cellular metabolism, cell viability, transwell migration, and the secretion of IL-1β, IL-6, and IL-10 were determined. In rabbits, after corneal de-epithelization, eye drops containing 0.002% and 1% KYNA were applied five times a day until full recovery. KYNA decreased metabolism but did not affect the proliferation of the corneal epithelium. It decreased both the metabolism and proliferation of conjunctival epithelium. KYNA enhanced the migration of corneal but not conjunctival epithelial cells. KYNA reduced the secretion of IL-1β and IL-6 from the corneal epithelium, leaving IL-10 secretion unaffected. The release of all studied cytokines from the conjunctival epithelium exposed to KYNA was unchanged. KYNA at higher concentration accelerated the healing of the corneal epithelium. These favorable properties of KYNA suggest that KYNA containing topical pharmaceutical products can be used in the treatment of ocular surface diseases.

Highlights

For the first time, we showed that Kynurenic acid (KYNA) accelerates the re-epithelization of experimentally induced corneal erosion in rabbits in vivo
Containing eye drops accelerated the process of re-epithelization 36 h after surgery, leading to an earlier full recovery of the corneal surface. This observation is consistent with the results of in vitro experiments in which KYNA promoted the migration of human corneal epithelium
We found that KYNA enhanced the release of IL-1β from corneal and conjunctival cells, and this result agreed with data, presenting an increased release of cytokines from the corneal epithelium during injuries [36]

Summary

Introduction

One of the most important challenges in modern ophthalmic pharmacology is how to accelerate the healing of corneal epithelial defects and prevent the migration of conjunctival epithelium onto the cornea. The reduction of pain and prevention of scarring of the conjunctiva after surgery (especially anti-glaucoma surgery) or trauma will be welcomed. Many attempts have been considered in topical therapy of ocular surface including blood derivatives [1], saliva [2], conditioned media from human amniotic epithelial cells [3], the growth hormone [4], and erythropoietin [5], albeit without satisfactory outcomes. 14, 753 x FOR PEER REVIEW Pharmaceuticals 22 of of 16. Many attempts have been considered in topical therapy of ocular surface including blood derivatives [1], saliva [2], conditioned media from human amniotic epithelial cells [3], the growth hormone [4], and erythropoietin [5], albeit without satisfactory outcomes. 4.0/).

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