Preventive and therapeutic effects of SkQ1-containing Visomitin eye drops against light-induced retinal degeneration

Abstract

The human retina is constantly affected by light of varying intensity, this being especially true for photoreceptor cells and retinal pigment epithelium. Traditionally, photoinduced damages of the retina are induced by visible light of high intensity in albino rats using the LIRD (light-induced retinal degeneration) model. This model allows study of pathological processes in the retina and the search for retinoprotectors preventing retinal photodamage. In addition, the etiology and mechanisms of retina damage in the LIRD model have much in common with the mechanisms of the development of age-related retinal disorders, in particular, with age-related macular degeneration (AMD). We have studied preventive and therapeutic effects of Visomitin eye drops (based on the mitochondria-targeted antioxidant SkQ1) on albino rat retinas damaged by bright light. In the first series of experiments, rats receiving Visomitin for two weeks prior to illumination demonstrated significantly less expressed atrophic and degenerative changes in the retina compared to animals receiving similar drops with no SkQ1. In the second series, the illuminated rats were treated for two weeks with Visomitin or similar drops without SkQ1. The damaged retinas of the experimental animals were repaired much more effectively than those of the control animals. Therefore, we conclude that Visomitin SkQ1-containing eye drops have pronounced preventive and therapeutic effects on the photodamaged retina and might be recommended as a photoprotector and a pharmaceutical preparation for the treatment of AMD in combination with conventional medicines.

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

“…The animal models of LIRD are generally acknowledged for AMD studies as they share many common features with the human disease (discussed in [3]). Consistently, we previously demonstrated that exposure of the eyes of experimental animals (rats and rabbits) to different doses of bright visible light leads to the development of retinal degenerative processes, including the apoptosis of photoreceptors and other retinal neurons, as well as vacuolization of RPE cells, their phagocytic activity, and migration into the neural retina, representing common hallmarks of AMD [3,14,15,43]. In the present study, we used a rabbit model of LIRD that was induced by intense short-term illumination (30,000 lx for 3 h) [3,15].…”

“…Interestingly, in previous LIRD studies, we have observed that focal signs of inflammation including disturbance in the blood-retinal barrier and inflammatory infiltration accompany the development of the degenerative changes in the retina. Indeed, retinal edema was found to already emerge at the early stages of LIRD, gradually expanding in the course of the disease and becoming complemented by granulocytic infiltration [14,43]. All of these signs were occasionally found in the model used in the current work, indicating that intraocular inflammation is a sustainable complication of LIRD.…”

“…Previously, we have developed a rabbit model of LIRD reproducing many aspects of AMD and other retinal degenerative diseases, such as apoptosis of photoreceptors and migration of RPE cells, as well as the breakdown of the blood-retinal barrier, leukocyte infiltration, edema, and other signs of intraocular inflammation [3,14,43]. These effects were accompanied by oxidative stress, which was efficiently prevented by premedication while using mitochondria-targeted antioxidant SkQ1 [3].…”

Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives

“…SkQ1 exhibits two-fold increased hydrogen peroxide inhibition potency compared with its derivative MitoQ1 61 . SkQ1 has been evaluated in vitro and in vivo and is currently approved as a droplet formulation (called Visomitin ® ) for eye diseases in Russia 108 .…”

Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant

“…Indeed, the essential features of human dry (non-neovascular) AMD can be reproduced in the models of light-induced retinal damage (LIRD) [15,16,17,18]. Our previous histological studies revealed that retinas of the animals exposed to various doses of light illumination exhibit such hallmarks of AMD as photoreceptor apoptosis, pigment epithelial cell migration into the neural retina, disturbance in blood-retinal barrier, and inflammatory infiltration [19,20]. The studies using these models may provide important information about general mechanisms of retinal photic damage underlying AMD and other degenerative retinal diseases.…”