Mitoquinone intravitreal injection ameliorates retinal ischemia-reperfusion injury in rats involving SIRT1/Notch1/NADPH axis.

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.

• Authors: Dongyong Tang, Xin Liu, Jun Chen
• Journal: Drug development research (Drug Dev Res) Vol. 83 Issue 3 Pg. 800-810 (05 2022) ISSN: 1098-2299 [Electronic] United States
• PMID: 35014081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley Periodicals, LLC.

Chemical References

• Notch1 protein, rat
• Organophosphorus Compounds
• Receptor, Notch1
• bcl-2-Associated X Protein
• Ubiquinone
• mitoquinone
• NADP
• Caspase 3
• Sirt1 protein, rat
• Sirtuin 1

Topics

• Animals
• Apoptosis
• Caspase 3 (metabolism)
• Intravitreal Injections
• NADP (metabolism, pharmacology, therapeutic use)
• Organophosphorus Compounds
• Oxidative Stress
• Rats
• Receptor, Notch1 (metabolism, therapeutic use)
• Reperfusion Injury (metabolism)
• Retina (metabolism, pathology)
• Sirtuin 1 (metabolism, pharmacology, therapeutic use)
• Ubiquinone (analogs & derivatives)
• bcl-2-Associated X Protein