Mitochondria-targeted antioxidant SKQ1 protects cornea from oxidative damage induced by ultraviolet irradiation and mechanical injury

Abstract

BackgroundCornea protects the eye against natural and anthropogenic ultraviolet (UV) damage and mechanical injury. Corneal incisions produced by UV lasers in ophthalmic surgeries are often complicated by oxidative stress and inflammation, which delay wound healing and result in vision deterioration. This study trialed a novel approach to prevention and treatment of iatrogenic corneal injuries using SkQ1, a mitochondria-targeted antioxidant approved for therapy of polyethiological dry eye disease.MethodsRabbit models of UV-induced and mechanical corneal damage were employed. The animals were premedicated or treated with conjunctival instillations of 7.5 μM SkQ1. Corneal damage was assessed by fluorescein staining and histological analysis. Oxidative stress in cornea was monitored by measuring malondialdehyde (MDA) using thiobarbituric acid assay. Total antioxidant activity (AOA) was determined using hemoglobin/H2O2/luminol assay. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured using colorimetric assays.ResultsIn both models corneas exhibited fluorescein-stained lesions, histologically manifesting as basal membrane denudation, apoptosis of keratocytes, and stromal edema, which were accompanied by oxidative stress as indicated by increase in lipid peroxidation and decline in AOA. The UV-induced lesions were more severe and long healing as corneal endothelium was involved and GPx and SOD were downregulated. The treatment inhibited loss of keratocytes and other cells, facilitated re-epithelialization and stromal remodeling, and reduced inflammatory infiltrations and edema thereby accelerating corneal healing approximately 2-fold. Meanwhile the premedication almost completely prevented development of UV-induced lesions. Both therapies reduced oxidative stress, but only premedication inhibited downregulation of the innate antioxidant activity of the cornea.ConclusionsSkQ1 efficiently prevents UV-induced corneal damage and enhances corneal wound healing after UV and mechanical impacts common to ocular surgery. Its therapeutic action can be attributed to suppression of mitochondrial oxidative stress, which in the first case embraces all corneal cells including epitheliocytes, while in the second case affects residual endothelial cells and stromal keratocytes actively working in wound healing. We suggest SkQ1 premedication to be used in ocular surgery for preventing iatrogenic complications in the cornea.

Analysis of aqueous humor total antioxidant capacity and its correlation with corneal endothelial health

“…Although the exact mechanism underlying this protective effect has not yet been elucidated, several in vitro and animal studies have suggested a relationship between free radical scavengers and reduced CEC damage. 43,44 Cestmir et al and Guo-Jian et al reported that antioxidants play an important role in the survival, healing, and migration of CEC. 45, double-blind clinical trial indicating that the use of dissolved H 2 in irrigation solution reduced corneal endothelial damage during phacoemulsification.…”

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

“…The total antioxidant activity in AH was analyzed via hemoglobin/H 2 O 2 /luminol system, as described in our previous works [68][69][70]. Briefly, the AH samples were diluted 200-fold with PBS and added to the reaction mixture, containing 0.01 mm luminol and 0.5 mm hemoglobin.…”

Advancements in therapeutic drugs targeting of senescence

“…130 It can also inhibit oxidative stress, effectively prevent damage caused by ultraviolet light, and promote corneal wound healing after eye surgery. 131 Collectively, these studies suggest that SKQ1 has the potential to become an effective antioxidant and a promising drug promoting healthy aging.…”