Mitochondrial Uncoupling Protein 2 Knock-out Promotes Mitophagy to Decrease Retinal Ganglion Cell Death in a Mouse Model of Glaucoma.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Daniel T Hass, Colin J Barnstable

Abstract

Glaucoma is a neurodegenerative disorder characterized by mitochondrial dysfunction and an increase in oxidative damage, leading to retinal ganglion cell (RGC) death. The oxidative status of RGCs is regulated intrinsically and also extrinsically by retinal glia. The mitochondrial uncoupling protein 2 (UCP2) relieves oxidative and neuronal damage in a variety of neurodegenerative disease models. We hypothesized that deletion of Ucp2 in either RGCs or retinal glia would increase retinal damage and RGC death in a mouse model of glaucoma. Paradoxically, we found the reverse, and deletion of mitochondrial Ucp2 decreased oxidative protein modification and reduced RGC death in male and female mice. This paradox was resolved after finding that Ucp2 deletion also increased levels of mitophagy in cell culture and retinal tissue. Our data suggest that Ucp2 deletion facilitates increased mitochondrial function by improving quality control. An increase in mitochondrial function explains the resistance of Ucp2-deleted retinas to glaucoma and may provide a therapeutic avenue for other chronic neurodegenerative conditions.SIGNIFICANCE STATEMENT Many unsolved neurodegenerative conditions result from defects in mitochondrial function. Molecular ...Continue Reading

Citations

May 12, 2020·Investigative Ophthalmology & Visual Science·Hannah YoungbloodYutao Liu
Mar 14, 2020·International Journal of Molecular Sciences·Ines RosignolPatricia Boya
Apr 29, 2020·Antioxidants·Elena B Domènech, Gemma Marfany
Mar 27, 2020·Frontiers in Cell and Developmental Biology·Annagrazia AdornettoRossella Russo
Jul 3, 2021·International Journal of Molecular Sciences·Anna FoschRosalía Rodríguez-Rodríguez
Aug 28, 2021·Frontiers in Cell and Developmental Biology·Jiahui TangYiqing Li

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