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

Autor: Zernii EY; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia. zerni@belozersky.msu.ru.; Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia. zerni@belozersky.msu.ru., Gancharova OS; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.; Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia., Tiulina VV; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia., Zamyatnin AA Jr; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.; Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia., Philippov PP; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia., Baksheeva VE; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia., Senin II; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia. senin@belozersky.msu.ru.
Jazyk: angličtina
Zdroj: BMC ophthalmology [BMC Ophthalmol] 2018 Dec 27; Vol. 18 (1), pp. 336. Date of Electronic Publication: 2018 Dec 27.
DOI: 10.1186/s12886-018-0996-7
Abstrakt: Background: Cornea 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.
Methods: Rabbit 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/H 2 O 2 /luminol assay. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured using colorimetric assays.
Results: In 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.
Conclusions: SkQ1 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.
Databáze: MEDLINE
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