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Mitochondria-Targeted Antioxidant SkQ1 Prevents Anesthesia-Induced Dry Eye Syndrome.

ABSTRACT: Dry eye syndrome (DES) is an age-related condition increasingly detected in younger people of risk groups, including patients who underwent ocular surgery or long-term general anesthesia. Being a multifactorial disease, it is characterized by oxidative stress in the cornea and commonly complicated by ocular surface inflammation. Polyetiologic DES is responsive to SkQ1, a mitochondria-targeted antioxidant suppressing age-related changes in the ocular tissues. Here, we demonstrate safety and efficacy of topical administration of SkQ1 at a dosage of 7.5 ?M for the prevention of general anesthesia-induced DES in rabbits. The protective action of SkQ1 improves clinical state of the ocular surface by inhibiting apoptotic and prenecrotic changes in the corneal epithelium. The underlying mechanism involves the suppression of the oxidative stress supported by the stimulation of intrinsic antioxidant activity and the activity of antioxidant enzymes, foremost glutathione peroxidase and glutathione reductase, in the cornea. Furthermore, SkQ1 increases antioxidant activity and stability of the tear film and produces anti-inflammatory effect exhibited as downregulation of TNF-? and IL-6 and pronounced upregulation of IL-10 in tears. Our data suggest novel features of SkQ1 and point to its feasibility in patients with DES and individuals at risk for the disease including those subjected to general anesthesia.

SUBMITTER: Zernii EY

PROVIDER: S-EPMC5660788 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Alzheimer's disease (AD) is the most common type of dementia, with increasing prevalence and no disease-modifying treatment available yet. There is increasing evidence-from interventions targeting mitochondria-that may shed some light on new strategies for the treatment of AD. Previously, using senescence-accelerated OXYS rats that simulate key characteristics of sporadic AD, we have shown that treatment with mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from age 12 to 18 months (that is, during active progression of AD-like pathology)-via improvement of mitochondrial function-prevented the neuronal loss and synaptic damage, enhanced neurotrophic supply, and decreased amyloid-β 1-42 protein levels and tau hyperphosphorylation in the hippocampus. In the present study, we continued to explore the mechanisms of the anti-AD effects of SkQ1 in an OXYS rat model through deep RNA sequencing (RNA-seq) and focused upon the cell-specific gene expression alterations in the hippocampus. According to RNA-seq results, OXYS rats had 1,159 differentially expressed genes (DEGs) relative to Wistar rats (control), and 6-month treatment with SkQ1 decreased their number twofold. We found that 10.5% of all DEGs in untreated (control) OXYS rats were associated with mitochondrial function, whereas SkQ1 eliminated differences in the expression of 76% of DEGs (93 from 122 genes). Using transcriptome approaches, we found that the anti-AD effects of SkQ1 are associated with an improvement of the activity of many signaling pathways and intracellular processes. SkQ1 changed the expression of genes in neuronal, glial, and endothelial cells, and these genes are related to mitochondrial function, neurotrophic and synaptic activity, calcium processes, immune and cerebrovascular systems, catabolism, degradation, and apoptosis. Thus, RNA-seq analysis yields a detailed picture of transcriptional changes during the development of AD-like pathology and can point to the molecular and genetic mechanisms of action of the agents (including SkQ1) holding promise for the prevention and treatment of AD.

Project description:BackgroundDry eye syndrome is a disorder of the tear film and is associated with symptoms of ocular discomfort. Punctal occlusion is a mechanical treatment in which the tear drainage system is blocked in order to aid in the preservation of natural tears on the ocular surface.ObjectivesThe objective of this review was to assess the safety and efficacy of punctal plugs for the management of dry eye.Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 6), MEDLINE (January 1950 to June 2010), EMBASE (January 1980 to June 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). We also searched the Science Citation Index-Expanded database and reference lists of included studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 21 June 2010.Selection criteriaWe included randomized and quasi-randomized controlled trials of collagen or silicone punctal plugs in symptomatic participants diagnosed with aqueous tear deficiency or dry eye syndrome.Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study investigators for additional information.Main resultsSeven randomized controlled trials including 305 participants (601 eyes) met the inclusion criteria and are summarized in this review. We did not perform meta-analysis due to appreciable variability in interventions and follow-up intervals. Although punctal plugs provided symptomatic improvement and clinical outcomes also improved from baseline measures, few studies demonstrated a benefit of punctal plugs over the comparison intervention. Reported adverse effects included epiphora (overflow of tears), foreign body sensation, eye irritation, and spontaneous plug loss.Authors' conclusionsThis systematic review shows a relative scarcity of controlled clinical trials assessing the efficacy of punctal occlusion therapy in dry eye. Although the evidence is very limited, the data suggest that silicone plugs can provide symptomatic relief in severe dry eye. Moreover, temporary collagen plugs appear similarly effective to silicone plugs on a short-term basis.

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Mitochondria-Targeted Antioxidant SkQ1 Prevents Anesthesia-Induced Dry Eye Syndrome.

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