[Mechanisms of perioperative corneal abrasions: alterations in tear film proteome]. / Mekhanizmy razvitiia perioperatsionnykh érozii rogovitsy: izmeneniia proteomnogo sostava sleznoi plenki.

Perioperative corneal abrasion is an ophthalmic complication commonly found in patients underwent general anesthesia. In this study, correlations between development of corneal injury and proteomic changes in tear film during general anesthesia were examined using an animal (rabbit) model. Being started after 1-h anesthesia, the process of accumulation of pathological changes in the cornea unequivocally led clinically significant abrasions following 3-6 h of the narcosis. The corneal damage was associated with alterations in profiles of major proteins of the tear film. Analysis of the tear proteome pointed to depression of lachrymal glands function, and suggested serotransferrin, serum albumin and annexin A1 as potential tear markers of the complication. The tear film alterations included fast drop of total antioxidant activity and activity of superoxide dismutase, and decrease in interleukin-4 and increase in interleukin-6 content indicating development of oxidative and pro-inflammatory responses. These findings suggest antioxidant and anti-inflammatory therapy as prospective approach for prevention/treatment of perioperative corneal abrasions. The observed anesthesia-induced effects should be considered in any study of ocular surface diseases employing anesthetized animals.

Alterations in Tear Biochemistry Associated with Postanesthetic Chronic Dry Eye Syndrome.

Perioperative dry eye syndrome (DES) is a common ocular complication of long-term general anesthesia. Chronic DES can lead to permanent damage to the cornea and disturbance of visual function, up to total loss of vision. Here, a relationship between the duration of general anesthesia and the risk of chronic DES in patients was demonstrated. Using an experimental model of perioperative corneal abrasions in rabbits, it was found that introduction of animals to 3-h general anesthesia resulted in clinically significant chronic damage to the cornea in 50% of cases. The development of the complication was not associated with irreversible or long-term impairment of tear secretion, but it was accompanied by a decrease in tear film stability and growth of the total protein content as well as decrease in total antioxidant activity of the tear induced by low molecular weight antioxidants. In addition, anesthesia-induced changes in activity of tear antioxidant enzymes including superoxide dismutase and enzymes providing homeostasis of reduced glutathione (glutathione peroxidase, glutathione-S-transferase, glutathione reductase) were observed. All these alterations were protracted (up to 1-2 weeks) and therefore might account for transition of the perioperative DES into the chronic form. These findings can be useful in the development of novel approaches for the prevention and treatment of chronic forms of DES in the postanesthetic period.

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind animals.

Mitochondria-targeted cationic plastoquinone derivative SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) has been investigated as a potential tool for treating a number of ROS-related ocular diseases. In OXYS rats suffering from a ROS-induced progeria, very small amounts of SkQ1 (50 nmol/kg per day) added to food were found to prevent development of age-induced cataract and retinopathies of the eye, lipid peroxidation and protein carbonylation in skeletal muscles, as well as a decrease in bone mineralization. Instillation of drops of 250 nM SkQ1 reversed cataract and retinopathies in 3-12-month-old (but not in 24-month-old) OXYS rats. In rabbits, experimental uveitis and glaucoma were induced by immunization with arrestin and injections of hydroxypropyl methyl cellulose to the eye anterior sector, respectively. Uveitis was found to be prevented or reversed by instillation of 250 nM SkQ1 drops (four drops per day). Development of glaucoma was retarded by drops of 5 microM SkQ1 (one drop daily). SkQ1 was tested in veterinarian practice. A totally of 271 animals (dogs, cats, and horses) suffering from retinopathies, uveitis, conjunctivitis, and cornea diseases were treated with drops of 250 nM SkQ1. In 242 cases, positive therapeutic effect was obvious. Among animals suffering from retinopathies, 89 were blind. In 67 cases, vision returned after SkQ1 treatment. In ex vivo studies of cultivated posterior retina sector, it was found that 20 nM SkQ1 strongly decreased macrophagal transformation of the retinal pigmented epithelial cells, an effect which might explain some of the above SkQ1 activities. It is concluded that low concentrations of SkQ1 are promising in treating retinopathies, cataract, uveitis, glaucoma, and some other ocular diseases.