Mitoquinone intravitreal injection ameliorates retinal ischemia–reperfusion injury in rats involvingSIRT1/Notch1/NADPHaxis

Abstract

Retinal ischemia–reperfusion injury (RIRI) is an important pathological process of many ocular diseases. Mitoquinone (MitoQ), a mitochondrial targeted antioxidant, is a potential compound for therapeutic development of RIRI. This study observed the effect of MitoQ on RIRI, and further explored its possible molecular mechanism. Temporary increase in intraocular pressure was used to establish rat model of RIRI to observe the effect of MitoQ treatment on retinal function, pathological injury, oxidative stress, inflammation and apoptosis. Immunohistochemistry and Western blot were used to detect expressions of cleaved caspase 3, B cell leukemia/lymphoma 2 associated X (Bax), nicotinamide adenine dinucleotide phosphate oxidase (NOX1), NOX4, cleaved‐Notch 1, hairy and enhancer of split 1 (Hes1), and sirtuin 1 (SIRT 1) in retina were detected by immunohistochemistry and Western blot. MitoQ treatment significantly improved retinal function and pathological injury, inhibited the over‐production of reactive oxygen species, increased the expression of superoxide dismutase 1 (SOD 1), suppressed the releases of inflammatory cytokines, and inhibited retinal cells apoptosis. MitoQ also down‐regulated the expressions of cleaved caspase 3, Bax, NOX 1, NOX 4, cleaved‐Notch 1, and Hes 1, increased the expression of SIRT 1 protein and its activity. These effects were significantly reversed by SIRT1 inhibitor EX527. Our data suggests that MitoQ, as a potentially effective drug for improving RIRI, may act through the SIRT1/Notch1/NADPH signal axis.

Mitochondria-Targeted Antioxidant Mitoquinone Maintains Mitochondrial Homeostasis through the Sirt3-Dependent Pathway to Mitigate Oxidative Damage Caused by Renal Ischemia/Reperfusion

“…MitoQ is one of the most widely studied mitochondria-targeted antioxidants, which can rapidly enter cells and accumulate in mitochondria, where it is converted into the active antioxidant panthenol form to participate in the antioxidant process [31]. Recent studies have confirmed that MitoQ plays an excellent protective role in ischemic diseases such as retinal ischemiareperfusion, renal transplantation, and intestinal ischemiareperfusion [32][33][34]. In the present study, we found that MitoQ significantly ameliorated renal dysfunction in I/R mice, which is consistent with an earlier study [18].…”

Long Noncoding RNA MIAT Modulates Chronic Retinal Ischemia-Reperfusion Injury in Mice via the microRNA-203-3p/SNAI2 Axis

“…2 Retinal IR injury (RIRI) is a major pathogenic mechanism of glaucoma, which is mostly unknown, containing neuroinflammation and neuronal death during pathological processes. 3 RIRI, a vital pathological process of multiple ocular diseases, 4 is a main reason for visual impairment or even blindness, and a useful and effective method to prevent visual decline needs to be further developed. 5 Inspired by that, we conducted this study to explore novel and efficient treatments.…”