RETINOPROTECTIVE EFFECT SkQ1 – VISOMITIN EYE DROPS – IS ASSOCIATED WITH SUPPRESSION p38MAPK AND ERK1/2 SIGNALING PATHWAYS ACTIVITY

Visomitin eye drops are the first and so far the only drug based on SkQ1 – the mitochondrial antioxidant 10-(6′-plastoquinonyl) decyltriphenylphosphonium, synthesized in the laboratories of Moscow State University under the leadership of Academician V.P. Skulachev. SkQ1 is considered as a potential tool to combat the aging program. We have previously shown that it is able to prevent and/or suppress the development of all manifestations of accelerated senescence in OXYS rats, including retinopathy, similar to age-related macular degeneration (AMD). Here, we assessed the effect of Visomitin instillations (from the age of 9 to 12 months) on the progression of AMD-like pathology and p38MAPK and ERK1/2 activity in OXYS rat retina. Wistar and OXYS rats treated with placebo (with a composition identical to Visomitin with the exception of SkQ1) used as controls. Ophthalmological examination showed that in OXYS rats receiving placebo, retinopathy progressed and the severity of clinical manifestations did not differ from intact OXYS rats. Visomitin suppressed the progression of AMD-like pathology in OXYS rats and significantly improved the structural and functional parameters of retinal pigment epithelium cells and the state of microcirculation in the choroid, which, presumably, contributed to the preservation of photoreceptors, associative and ganglion neurons. It was found that the activity of p38MAPK and ERK1/2 in the retina of 12-month-old OXYS rats is higher than that of Wistar rats of the same age, as indicated by the increased content of phosphorylated forms of p38MAPK and ERK1/2 and their target protein tau (at position T181 and S396). Visomitin decreased the phosphorylation of p38MAPK, ERK1/2 and tau, indicating suppression of the activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress the progression of AMD-like pathology in OXYS rats and their effect is associated with a decrease in the activity of MAPK signaling cascades.