Journal
PROGRESS IN RETINAL AND EYE RESEARCH
Volume 83, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.preteyeres.2021.100941
Keywords
Retina; Reactive oxygen species (ROS); Uncoupling; UCP; Mitochondria; Neuroprotection
Categories
Funding
- National Institutes of Health [NS100508, EY 029992, EY 007031]
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Oxidative stress is a crucial factor in major retinal diseases, with mitochondria being a significant source of reactive oxygen species (ROS). UCP2, as a member of the mitochondrial uncoupling protein family, can modulate ROS production and increase neuroprotection in various diseases, making it a promising therapeutic target. Studies on UCP2 have revealed its structural mechanism of action and ways to control its expression and activity for therapeutic use in both acute and chronic conditions, providing new tools to combat serious retinal diseases.
Oxidative stress is a major component of most major retinal diseases. Many extrinsic anti-oxidative strategies have been insufficient at counteracting one of the predominant intrinsic sources of reactive oxygen species (ROS), mitochondria. The proton gradient across the inner mitochondrial membrane is a key driving force for mitochondrial ROS production, and this gradient can be modulated by members of the mitochondrial uncoupling protein (UCP) family. Of the UCPs, UCP2 shows a widespread distribution and has been shown to uncouple oxidative phosphorylation, with concomitant decreases in ROS production. Genetic studies using transgenic and knockout mice have documented the ability of increased UCP2 activity to provide neuroprotection in models of a number of diseases, including retinal diseases, indicating that it is a strong candidate for a therapeutic target. Molecular studies have identified the structural mechanism of action of UCP2 and have detailed the ways in which its expression and activity can be controlled at the transcriptional, translational and posttranslational levels. These studies suggest a number of ways in control of UCP2 expression and activity can be used therapeutically for both acute and chronic conditions. The development of such therapeutic approaches will greatly increase the tools available to combat a broad range of serious retinal diseases.
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