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Cited by 10Retinal Development and DisordersGlaucoma and retinal disordersRetinal Diseases and Treatments

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

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Nsiah, Nana Yaa, Inman, Denise M.·2022·Cells
DOI 10.3390/cells11233756PMC PMC9737073
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Abstract

Müller 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.

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  • Metabolic stress that increases glycolytic metabolism and LDHA expression in other systems did not induce LDH expression in mature Cox10-deficient oligodendrocytes.

    “Interestingly, metabolic stress that increases glycolytic metabolism and LDHA expression in other systems, including mitochondrial dysfunction in mice with Cox10-deficiency in neurons or Müller cells (Garcia et al., 2022;Nsiah & Inman, 2022), did not induce LDH expression in mature Cox10-deficient oligodendrocytes (Figure 4e), revealing a remarkable lack of metabolic plasticity.”

    From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Nsiah & Inman, 2022

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Cited by

Sorted by citations

Authors
Nsiah, N. Y., & Inman, D. M.
Affiliations
University of North Texas Health Science Center (US)
Corresponding author
Inman, Denise M.
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2022-11-24
Volume
11
Issue
23
Pages
3756
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells11233756
PMC
PMC9737073
OpenAlex
W4309855192
Cited by
10
References
5
Citations by year
2026: 2 · 2025: 6 · 2024: 2
FWCI
0.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Eye Institute (EY026662)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
Müller cells, cytochrome c oxidase, cytochrome c oxidase subunit IV, COX10, ocular hypertension, hypoxia response, oxidative phosphorylation, mitochondrial respiration, oxidative stress, scotopic electroretinogram, retinal ganglion cell death, retinal metabolism, knockout mice
MeSH terms
Animals, Electron Transport Complex IV, Electroretinography, Glaucoma, Membrane Proteins, Neuroglia, Ocular Hypertension, Retina, Mice, Knockout, Alkyl and Aryl Transferases, Mice

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