Destabilizing COXIV in Muller Glia Increases Retinal Glycolysis and Alters Scotopic Electroretinogram

Simple item page
dc.creatorNsiah, Nana Yaa
dc.creatorInman, Denise M.
dc.creator.orcid0000-0002-8522-4112 (Inman, Denise M.)
dc.date.accessioned2023-02-07T21:55:46Z
dc.date.available2023-02-07T21:55:46Z
dc.date.issued2022-12-12
dc.description.abstractMuller glia (MG), the principal glial cell of the retina, have a metabolism that defies categorization into glycolytic versus oxidative. We showed that MG mount a strong hypoxia response to ocular hypertension, raising the question of their relative reliance on mitochondria for function. To explore the role of oxidative phosphorylation (OXPHOS) in MG energy production in vivo, we generated and characterized adult mice in which MG have impaired cytochrome c oxidase (COXIV) activity through knockout of the COXIV constituent COX10. Histochemistry and protein analysis showed that COXIV protein levels were significantly lower in knockout mouse retina compared to control. Loss of COXIV activity in MG did not induce structural abnormalities, though oxidative stress was increased. Electroretinography assessment showed that knocking out COX10 significantly impaired scotopic a- and b-wave responses. Inhibiting mitochondrial respiration in MG also altered the retinal glycolytic profile. However, blocking OXPHOS in MG did not significantly exacerbate retinal ganglion cell (RGC) loss or photopic negative response after ocular hypertension (OHT). These results suggest that MG were able to compensate for reduced COXIV stability by maintaining fundamental processes, but changes in retinal physiology and metabolism-associated proteins indicate subtle changes in MG function.
dc.description.sponsorshipThis research was funded by the National Eye Institute, grant number EY026662.
dc.identifier.citationNsiah, N. Y., & Inman, D. M. (2022). Destabilizing COXIV in Müller Glia Increases Retinal Glycolysis and Alters Scotopic Electroretinogram. Cells, 11(23), 3756. https://doi.org/10.3390/cells11233756
dc.identifier.issn2073-4409
dc.identifier.issue23
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32009
dc.identifier.volume11
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cells11233756
dc.rights.holder© 2022 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCells
dc.subjectMuller glia
dc.subjectelectroretinogram
dc.subjectglaucoma
dc.subjectglycolysis
dc.subjectmetabolism
dc.subjectoxidative phosphorylation
dc.subject.meshMice
dc.subject.meshAnimals
dc.subject.meshElectron Transport Complex IV / metabolism
dc.subject.meshElectroretinography
dc.subject.meshRetina / metabolism
dc.subject.meshOcular Hypertension / metabolism
dc.subject.meshGlaucoma / metabolism
dc.subject.meshNeuroglia / metabolism
dc.subject.meshMice,
dc.subject.meshKnockout
dc.subject.meshMembrane Proteins / metabolism
dc.subject.meshAlkyl and Aryl Transferases / metabolism
dc.titleDestabilizing COXIV in Muller Glia Increases Retinal Glycolysis and Alters Scotopic Electroretinogram
dc.typeArticle
dc.type.materialtext

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
full text article
Size:
7.37 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Publications -- Denise Inman