New antioxidant SkQ1 is an effective protector of rat eye retinal pigment epithelium and choroid under conditions of long-term organotypic cultivation

Abstract

Cells have intrinsic mechanisms for cleaning harmful oxidants represented mainly by reactive oxygen species (ROS). Despite the antioxidant defense, ROS can cause serious damage to the retina that with age leads to various eye diseases and even blindness. Among numerous cell sites of ROS generation, mitochondrial electron transport is of crucial importance. Recently, for the purpose of cleaning ROS in the mitochondrial matrix, powerful mitochondria-targeted antioxidant "SkQ1" has been invented. We studied SkQ1 effects upon tissues of rat posterior eye cup that consisted: retinal pigment epithelium (RPE) ↔ choroidal coat ↔ scleral coat. The eye cups were isolated from the eyes of adult albino rats and cultivated in rotary tissue culture system in the presence of 20 nM SkQ1 or without this compound. After 7 days -1 month in vitro eye cup samples were studied by immunohistochemistry, routine histology, morphometry, and digital image analysis. We have found that under chosen, "in vitro like in vivo" conditions 20 nM SkQ1 effectively reduced cell death in RPE and choroid, protected RPE from disintegration caused by cell phenotypic transformation and withdrawal from the layer, suppressed transmigration of choroidal coat cells. In the ex vivo model we used degenerative processes were more pronounced in the eye cup center where SkQ1 effect was most vivid. All this give us hopes for effectiveness of SkQ1 treatment of retinal central part that is very susceptible to light-induced over-oxidation injury and mostly suffering in many age-related diseases, AMD, in particular.

New antioxidant SkQ1 is an effective protector of rat neural retina under conditions of long-term organotypic cultivation

“…In our previous study, we have demonstrated the protective effects of the novel penetrating cation 10-(6'plastoquinonyl) decyltriphenylphosphonium, SkQ1, upon RPE and choroid under the conditions of a long-term organotypic culturing of eye posterior cup [13]. Now we have found that 20 nM SkQ1 conserves the native structure and decreases cell death of NR cultivated in the content of eye posterior cup under similar ex vivo experimental conditions.…”

“…The analysis of NR in the content of eye posterior cups was performed after 7, 14 and 30 days of in vitro culturing in a roller, with or without SkQ1 in the medium. 20 nM concentration of SkQ1 was used since previously it inserted positive effects on rat eye tissue viability [13].…”

“…Compound SkQ1 was synthesized as described in [7]. In our study as in the previous work [13] we used 20 nM SkQ1, the concentration most effective in comparison with others, higher concentrations (units or hundreds of nM) which were tested preliminary.…”

“…In a number of the in vitro and in vivo models [7,[9][10][11] it has been demonstrated that SkQ1 possesses a powerful antioxidant activity, owing to its ability to clean the matrix space of mitochondria, "the dirtiest place in the cell" in respect of ROS [12]. Recently, we have described the protective effect of SkQ1 upon maintaining of cell morphology and viability in RPE and choroid in the content of the rat posterior eye cup under conditions of long-term, organotypic, rotary cultivation [13]. In this study, we employed a similar method to study SkQ1 effect upon NR in the content of rat posterior eye cup.…”

Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective

“…At present, neuroprotection strategies aimed at mobilizing endogenous defense systems and enhancing the antioxidant defense of RPE cells remain the most effective [ 272 , 273 , 274 , 275 ]. The RPE is closely associated with the neural part of the retina; therefore, the restoration of photoreceptor functions protects the RPE from OS and vice versa, where the protection of the RPE from OS prevents degenerative changes in the retina.…”