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 … Show more
“…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.…”
Section: Discussionmentioning
confidence: 82%
“…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].…”
Section: Resultsmentioning
confidence: 99%
“…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.…”
Section: Methodsmentioning
confidence: 99%
“…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.…”
During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)-the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 has recently been invented to reduce mitochondrial ROS by cleaning the mitochondria matrix, "the dirtiest place in the cell" in respect of ROS production and accumulation. Earlier we studied SkQ1 effects upon retinal pigment epithelium and choroid in the rat eye posterior cups exposed to long-term 3D organotypic culturing. It was found that under in vitro conditions 20 nM SkQ1 effectively reduced cell death in retinal pigment epithelium and choroid and protected the tissues from disintegration and cell withdrawal. In the present study we used same ex vivo conditions to examine the effect of SkQ1 upon the rat neural retina kept in the content of the posterior eye cup. Eye cups were isolated and cultured in vitro during 7, 14, and 30 days under rotation in the presence and absence of 20 nM SkQ1 in the culture medium. Serial sections of cultivated eye cups were subjected to histology, computer morphometry and immunohistochemistry. Obtained results show that SkQ1 operates as a strong protective agent, preventing neuronal cell death and other degenerative processes in the neural retina. Cell rescue by SkQ1 was more vivid in the central part of the retina than at the periphery. That, in turn, suggests SkQ1 effectiveness in treatment of some age-related eye diseases when central part of the retina, including macula, is most susceptible to degeneration.
“…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.…”
Section: Discussionmentioning
confidence: 82%
“…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].…”
Section: Resultsmentioning
confidence: 99%
“…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.…”
Section: Methodsmentioning
confidence: 99%
“…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.…”
During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)-the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 has recently been invented to reduce mitochondrial ROS by cleaning the mitochondria matrix, "the dirtiest place in the cell" in respect of ROS production and accumulation. Earlier we studied SkQ1 effects upon retinal pigment epithelium and choroid in the rat eye posterior cups exposed to long-term 3D organotypic culturing. It was found that under in vitro conditions 20 nM SkQ1 effectively reduced cell death in retinal pigment epithelium and choroid and protected the tissues from disintegration and cell withdrawal. In the present study we used same ex vivo conditions to examine the effect of SkQ1 upon the rat neural retina kept in the content of the posterior eye cup. Eye cups were isolated and cultured in vitro during 7, 14, and 30 days under rotation in the presence and absence of 20 nM SkQ1 in the culture medium. Serial sections of cultivated eye cups were subjected to histology, computer morphometry and immunohistochemistry. Obtained results show that SkQ1 operates as a strong protective agent, preventing neuronal cell death and other degenerative processes in the neural retina. Cell rescue by SkQ1 was more vivid in the central part of the retina than at the periphery. That, in turn, suggests SkQ1 effectiveness in treatment of some age-related eye diseases when central part of the retina, including macula, is most susceptible to degeneration.
“…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.…”
Section: The Exogenous Regulation Of Redox Homeostasis Of Rpe Cellsmentioning
The retinal pigment epithelium (RPE) performs a range of necessary functions within the neural layers of the retina and helps ensure vision. The regulation of pro-oxidative and antioxidant processes is the basis for maintaining RPE homeostasis and preventing retinal degenerative processes. Long-term stable changes in the redox balance under the influence of endogenous or exogenous factors can lead to oxidative stress (OS) and the development of a number of retinal pathologies associated with RPE dysfunction, and can eventually lead to vision loss. Reparative autophagy, ubiquitin–proteasome utilization, the repair of damaged proteins, and the maintenance of their conformational structure are important interrelated mechanisms of the endogenous defense system that protects against oxidative damage. Antioxidant protection of RPE cells is realized as a result of the activity of specific transcription factors, a large group of enzymes, chaperone proteins, etc., which form many signaling pathways in the RPE and the retina. Here, we discuss the role of the key components of the antioxidant defense system (ADS) in the cellular response of the RPE against OS. Understanding the role and interactions of OS mediators and the components of the ADS contributes to the formation of ideas about the subtle mechanisms in the regulation of RPE cellular functions and prospects for experimental approaches to restore RPE functions.
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