ABSTRACT
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.
Subject(s)
Aging , Eye Diseases/veterinary , Mitochondria/metabolism , Plastoquinone/analogs & derivatives , Animals , Biological Transport , Blindness/drug therapy , Blindness/physiopathology , Blindness/veterinary , Cats , Dogs , Eye Diseases/drug therapy , Eye Diseases/physiopathology , Eye Diseases/prevention & control , Female , Horses , In Vitro Techniques , Male , Mitochondria/chemistry , Mitochondria/drug effects , Plastoquinone/metabolism , Plastoquinone/pharmacology , Progeria/chemically induced , Progeria/physiopathology , Progeria/veterinary , Rabbits , Rats , Reactive Oxygen Species/metabolism , Retina/drug effects , Retina/metabolism , Retina/physiopathologyABSTRACT
It has been shown by biochemical analysis and differential scanning calorimetry that the connective tissue formed around a transplant as a result of sclero-reinforcing interference (capsula) is similar to intact sclera. The main component of newly formed capsules is collagen I whose fibers have a perfect structure and the amount of cross-links sufficient to provide normal thermomechanical properties. A fraction of collagen having thermally labile "immature" cross-links in capsules formed around the transplant impregraned with Panaxal has been detected by differential scanning calorimetry. It was suggested that fibroblasts in tissues of these capsules have a high synthetic activity.