Zernii Evgeni Yu, Gancharova Olga S, Tiulina Veronika V, Zamyatnin Andrey A, Philippov Pavel P, Baksheeva Viktoriia E, Senin Ivan I
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.
BMC Ophthalmol. 2018 Dec 27;18(1):336. doi: 10.1186/s12886-018-0996-7.
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.
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/HO/luminol assay. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured using colorimetric assays.
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.
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.
角膜可保护眼睛免受自然和人为紫外线（UV）损伤以及机械性损伤。眼科手术中紫外线激光造成的角膜切口常因氧化应激和炎症而变得复杂，这会延迟伤口愈合并导致视力下降。本研究尝试了一种使用SkQ1预防和治疗医源性角膜损伤的新方法，SkQ1是一种经批准用于治疗多种病因所致干眼症的线粒体靶向抗氧化剂。
采用紫外线诱导和机械性角膜损伤的兔模型。动物通过结膜滴注7.5 μM SkQ1进行预处理或治疗。通过荧光素染色和组织学分析评估角膜损伤。使用硫代巴比妥酸法测量丙二醛（MDA）来监测角膜中的氧化应激。使用血红蛋白/血红素加氧酶/鲁米诺法测定总抗氧化活性（AOA）。使用比色法测量谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活性。
在两种模型中，角膜均出现荧光素染色的病变，组织学表现为基底膜剥脱、角膜细胞凋亡和基质水肿，同时伴随着脂质过氧化增加和AOA下降所表明的氧化应激。由于角膜内皮受累且GPx和SOD下调，紫外线诱导的病变更严重且愈合时间更长。该治疗抑制了角膜细胞和其他细胞的丢失，促进了上皮再形成和基质重塑，并减少了炎症浸润和水肿，从而使角膜愈合加速约2倍。同时，预处理几乎完全防止了紫外线诱导病变的发生。两种治疗方法均降低了氧化应激，但只有预处理抑制了角膜固有抗氧化活性的下调。
SkQ1能有效预防紫外线诱导的角膜损伤，并增强紫外线和眼科手术常见的机械冲击后角膜伤口的愈合。其治疗作用可归因于对线粒体氧化应激的抑制，在第一种情况下，这种抑制作用涵盖了包括上皮细胞在内的所有角膜细胞，而在第二种情况下，它影响在伤口愈合中积极发挥作用的残余内皮细胞和基质角膜细胞。我们建议在眼科手术中使用SkQ1预处理来预防角膜医源性并发症。
