Biomarkers of Oxidative Stress and Cataract. Novel Drug Delivery Therapeutic Strategies Targeting Telomere Reduction and the Expression of Telomerase Activity in the Lens Epithelial Cells with N-Acetylcarnosine Lubricant Eye Drops: Anti-Cataract which Helps to Prevent and Treat Cataracts in the Eyes of Dogs and other Animals

Mark   A.   Babizhayev; Yegor   E.   Yegorov

doi:10.2174/15672018113106660062

Abstract

Cataracts in Small Animals are shown to be at least partially caused by oxidative damage to lens epithelial cells (LECs) and the internal lens; biomarkers of oxidative stress in the lens are considered as general biomarkers for life expectancy in the canine and other animals. Telomeres lengths and expressed telomerase activity in canine LECs may serve as important monitors of oxidative damage in normal LECs with documented higher levels of telomerase activity in cataractous LECs during cells’ lifespan. Loss of functional telomere length below a critical threshold in LECs of canines during the effect of UV and chronic oxidative stress or metabolic failure, can activate programs leading to LEC senescence or death. Telomerase is induced in LECs of canines at critical stages of cataractogenesis initiation and exposure to oxidative stress through the involvement of catalytically active prooxidant transition metal (iron) ions. This work documents that transition metal ions (such as, ferrous ions- catalytic oxidants) might induce premature senescence in LECs of canines, telomere shortening with increased telomerase activity as adaptive response to UV light, oxidative and metabolic stresses. The therapeutic treatment with 1% N-acetylcarnosine (NAC) prodrug delivery is beneficial for prevention and dissolution of ripe cataracts in canines. This biological activity is based on the findings of ferroxidase activity pertinent to the dipeptide carnosine released ophthalmically from NAC prodrug of L-carnosine, stabilizing properties of carnosine on biological membranes based on the ability of the imidazole-containing dipeptides to interact with lipid peroxidation products and reactive oxygen species (ROS), to prevent membrane damage and delute the associated with membrane fragements protein aggregates. The advent of therapeutic treatment of cataracts in canines with N-acetylcarnosine lubricant eye drops through targeting the prevention of loss of functional telomere length below a critical threshold and “flirting” with an indirect effect with telomerase expression in LECs of canines during the effects of UV, chronic oxidative stress increases the successful rate of cataract management challenges in home veterinary care.

Keywords: Aging and cataract, biological marker, carnosine, cataract treatment in canines, ferritin, ferroxidase activity, L-carnosine as universal antioxidant, lens epithelial cells, lifespan, N-acetylcarnosine ophthalmic prodrug, oxidative stress, small animals, transition metal (ferrous) ions, telomerase activity, telomere-dependent senescent phenotype, telomere shortening.