Mitochondrial uncoupling protein 2 knock-out promotes mitophagy to decrease retinal ganglion cell death in a mouse model of glaucoma

Daniel T. Hass, Colin Barnstable

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3582-3596
Number of pages15
JournalJournal of Neuroscience
Volume39
Issue number18
DOIs
StatePublished - May 1 2019

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Mitochondrial Degradation
Retinal Ganglion Cells
Glaucoma
Cell Death
Neuroglia
Neurodegenerative Diseases
Quality Control
Retina
Cell Culture Techniques
Uncoupling Protein 2
Proteins
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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Mitochondrial uncoupling protein 2 knock-out promotes mitophagy to decrease retinal ganglion cell death in a mouse model of glaucoma. / Hass, Daniel T.; Barnstable, Colin.

In: Journal of Neuroscience, Vol. 39, No. 18, 01.05.2019, p. 3582-3596.

Research output: Contribution to journalArticle

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