Abstract：
Visomitin eye drops are the first and, so far, the only drug based on SkQ1 - the mitochondria-targeted antioxidant 10-(6\'-plastoquinonyl) decyltriphenylphosphonium, developed 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 development of all manifestations of accelerated senescence in OXYS rats, including retinopathy, similar to the age-related macular degeneration (AMD). Here, we assessed the effect of Visomitin instillations on progression of the AMD-like pathology and p38 MAPK and ERK1/2 activity in the OXYS rat retina (from the age of 9 to 12 months). Wistar and OXYS rats treated with placebo (composition identical to Visomitin with the exception of SkQ1) were used as controls. Ophthalmological examination showed that in the OXYS rats receiving placebo, retinopathy progressed and severity of clinical manifestations did not differ from the intact OXYS rats. Visomitin suppressed progression of the AMD-like pathology in the OXYS rats and significantly improved structural and functional parameters of the retinal pigment epithelium cells and state of microcirculation in the choroid, which, presumably, contributed to preservation of photoreceptors, associative and ganglion neurons. It was found that the activity of p38 MAPK and ERK1/2 in the retina of 12-month-old OXYS rats is higher than that of the Wistar rats of the same age, as indicated by the increased content of phosphorylated forms of p38 MAPK and ERK1/2 and their target protein tau (at position T181 and S396). Visomitin decreased phosphorylation of p38 MAPK, ERK1/2, and tau indicating suppression of activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress progression of the AMD-like pathology in the OXYS rats and their effect is associated with the decrease in activity of the MAPK signaling cascades.
摘要：
Visomitin眼药水是第一个，到目前为止,基于SkQ1的唯一药物-线粒体靶向抗氧化剂10-（6'-plastoquinonyl）癸基三苯基膦，在V.P.Skulachev院士的领导下在莫斯科国立大学的实验室开发。SkQ1被认为是对抗衰老计划的潜在工具。我们以前已经表明，它能够预防和/或抑制OXYS大鼠加速衰老的所有表现的发展，包括视网膜病变,与年龄相关性黄斑变性（AMD）相似。这里,我们评估了Visomitin滴注对OXYS大鼠视网膜(9~12月龄)AMD样病变进展以及p38MAPK和ERK1/2活性的影响.用安慰剂(除了SkQ1之外,与Visomitin相同的组合物)处理的Wistar和OXYS大鼠用作对照。眼科检查显示，在接受安慰剂的OXYS大鼠中，视网膜病变进展，临床表现的严重程度与完整的OXYS大鼠没有差异。Visomitin抑制了OXYS大鼠AMD样病理的进展，并显着改善了视网膜色素上皮细胞的结构和功能参数以及脉络膜中的微循环状态，which,据推测,有助于保护光感受器，联想和神经节神经元。发现12月龄OXYS大鼠视网膜中p38MAPK和ERK1/2的活性高于同龄Wistar大鼠,如p38MAPK和ERK1/2的磷酸化形式及其靶蛋白tau（在位置T181和S396）的含量增加所示。Visomitin降低p38MAPK的磷酸化，ERK1/2和tau指示这些MAPK信号传导级联的活性的抑制。因此，Visomitin滴眼液能够抑制OXYS大鼠中AMD样病理的进展,并且它们的作用与MAPK信号传导级联的活性降低相关。
