The Role of SKQ1 (Visomitin) in Inflammation and Wound Healing of the Ocular Surface

INTRODUCTION: SkQ1 (Visomitin) is a novel mitochondrial-targeted antioxidant that holds promise in the treatment of inflammation associated with ocular surface diseases such as dry eye disease (DED) and corneal wounds. However, the specific role of SkQ1 in ocular surface epithelial tissue has yet to be explicated. The goal of this study is to identify roles of SkQ1 in conjunctival inflammation and corneal wound healing. METHODS: To determine the role of SkQ1 in inflammation, human conjunctival epithelial (HCjE) cell cultures were sensitized with pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) followed by treatments with SkQ1. The production of inflammatory biomarker prostaglandin E2 (PGE2) and cell viability were quantitatively evaluated. To determine the role of SkQ1 in wound healing, human corneal limbus epithelial (HCLE) cell cultures were streaked to create wounds. The wound closure times, ability to support single HCLE cell proliferation and changes of cell migration in the presence of SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), were further compared. RESULTS: The HCjE and HCLE cultures showed no apparent cytotoxicity to SkQ1 in concentrations up to 250 nM (HCjE) or 2500 nM (HCLE). The HCLE cultures showed no toxicity to SkQ1 at all the SkQ1 concentrations tested. SkQ1 significantly suppressed PGE2 production of HCjE at concentrations < 300 nM (24 h) and 50 nM (48 h), apparently being SkQ1 dose and treatment time dependent. The wound closure rates were increased by 4% in 4 h and by 9% after 8–12 h in the presence of 50 nM SkQ1. Furthermore, as little as 25 nM of SkQ1 significantly stimulated HCLE single-cell proliferation. Lastly, the SkQ1-stimulated wound healing was completely abolished by SB203580. CONCLUSION: Results of the current study demonstrate that SkQ1 exhibits an anti-inflammatory role and can be safely applied to ocular surface epithelium up to a concentration of 300 nM (181 ng/ml) for 24 h. SkQ1 also significantly enhances corneal epithelial wound healing, likely through enhancement of cell proliferation and migration. The data provide solid support for SkQ1 as a promising new therapeutic strategy for treatment of conjunctival inflammation as well as corneal wounds. FUNDING: This study was sponsored by Mitotech SA Pharmaceuticals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40123-018-0158-2) contains supplementary material, which is available to authorized users.