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 μM 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-α 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.

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.…”

Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

“…The pathological changes of mitochondrial-related dysfunctions, including accumulation of ROS and superoxide in the mitochondria and MMP (△Ψm) reduction, were discovered in AMD [25]. In other mitochondrial targeting compounds [10,14,31], we observed that pretreatment with TPP-Niacin signi cantly enhanced the MMP and improved the mitochondrial ultrastructure in a phenotypic analysis by EM, compared to H 2 O 2 alone. Based on these data, we next analyzed the expressions of mitochondria-related genes, such as OXPHOS subunits, mitochondrial dynamics, and mitochondrial DNA replication and transcription genes.…”

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

“…DES affects up to 40% of the adult population and manifests as eye irritation, hyperemia, glare, eye fatigue, and blurred vision [2,3]. Etiologically, alterations in tear homeostasis are associated with dysfunction of the lachrymal and/or Meibomian glands (such as in Sjögren syndrome and Meibomian Gland Dysfunction (MGD)) as well as a number of other factors, including contact lens wearing, adverse effects of various medications, complications of ocular surgery and general anesthesia [1,[4][5][6][7].…”

“…thereby providing local antioxidant defense [17,18]. Accordingly, the inflammatory component of DES can be attenuated by the topical administration of antioxidants [6,19].…”