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

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.

Determination of Bioactive Compound Kynurenic Acid in Linum usitatissimum L.

“…It should be pointed out that KYNA is a beneficial compound in wound healing, since it was reported that KYNA prevents scarring and may be used as an anti-fibrogenic agent [10]. It was proved that kynurenine and its derivatives (e.g., KYNA) might be considered as effective wound healing agents in a rabbit ear scar model [11,12] Since KYNA has established health-promoting properties but its content in food is relatively low [1], a search to identify rich sources of natural KYNA is in progress. The obtained results indicate that the tested flax cultivars contained a maximum of 0.4 µg/g FW KYNA in the seeds.…”

“…Since obesity and cardiovascular diseases constitute increasing health problems in developing societies, it is justifiable to search for natural products that are effective in the prevention and treatment of these diseases. On the other hand, it was stated that KYNA improves the healing of skin wounds [10][11][12] and prevents the formation of scars [10]. Thus, two aspects of KYNA application should be considered: its systemic effect on the human body (e.g., on the digestive system) and its local action (e.g., for wound healing).…”

Metabolomics in Corneal Diseases: A Narrative Review from Clinical Aspects

“…In T1DM, there was an upregulation of xanthurenic acid and kynurenic acid in the corneal stroma, suggesting dysregulation of kynurenine metabolism. Kynurenic acid is known to have antioxidant, anti-inflammatory, and anti-proliferative properties [ 99 , 100 ] and the kynurenine pathway has been linked to corneal endothelium health [ 101 ]. In T2DM, however, there was no increase in kynurenic acid and xanthurenic acid but a significant increase in nicotinate levels due to the modulation of tryptophan metabolism, with no increase in the metabolites in the kynurenine pathway.…”

A Review of the Health Benefits of Food Enriched with Kynurenic Acid

“…The beneficial wound healing effects of KYNA ( Table S7 ) after its external administration on the skin and cornea in rabbits are also worth mentioning [ 104 , 105 ]. It is worth noting that a clinical trial with the use of 0.5% KYNA dressing in people with skin scarring has already been successfully completed [ 106 ].…”

“…Detailed data on the health-promoting effects of KYNA administration in animals regardless of the route of administration are presented in Table S7 [ 26 , 87 , 90 , 93 , 94 , 95 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ].…”