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

Abstract

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.

Organotypic culture of neural retina as a research model of neurodegeneration of ganglion cells

“…In addition, this model as well as approaches using neural retinal explants [24] can be used for screening of new retino and neuroprotectors. For example, the method of organotypic roller cultivation of retina of the rat eye posterior segment has been recently used to study the protective effect of the new antioxidant SkQ1 [25,26] on cells of degenerating retina [27]. In this research, it was shown that very low SkQ1 concentration (20 nM) effectively prevents retinal cell death and main tains cytoarchitectonics of retinal layers, including its ganglion cell layer.…”

Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes

“…Since transplantation of exogenous cellular sources for the retina is not always successful, endogenous stimulation has many advantages. In this regard, the search continues for opportunities to stimulate potential endogenous cellular sources, directing control of the differentiation of cells to restore tissue and the normal functioning of the organ of vision [360][361][362]. Studies show that in damaged neurons of the retina, activation of the transcription program is observed, which promotes initial recovery and partial restoration of function.…”