Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma.

Title

Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma.

Creator

Jassim AH; Fan Y; Pappenhagen N; Nsiah NY; Inman DM

Publisher

Antioxidants & Redox Signaling

Date

2021
2021-04-29

Description

Aims: Cellular response to hypoxia can include transition from respiration to glycolysis via upregulation of glycolytic enzymes and transporters, as well as mitophagy induction to eliminate surplus mitochondria. Our purpose was to evaluate the impact of hypoxia-inducible factor-1α (HIF-1α) stabilization on mitochondrial homeostasis and oxidative stress in a chronic model of glaucoma. Results: Retina and optic nerve (ON) were evaluated from young and aged DBA/2J (D2) glaucoma model mice and the control strain, the DBA/2- Gpnmb + . Hypoxic retinal ganglion cells (RGCs) were observed in young and aged D2 retina, with a significant increase in HIF-1α protein in the aged D2 retina. Reactive oxygen species observed in young D2 retina and ON were followed by significant decreases in antioxidant capacity in aged D2 retina and ON. HIF-1α targets such as neuron-specific glucose transporter-3 and lactate dehydrogenase were decreased or unchanged, respectively, in aged D2 retina despite an increased hypoxia response in RGCs. Mitochondrial mass was decreased in aged D2 retina concomitant with decreased mitochondrially encoded electron transport chain transcripts despite a stable nuclear-encoded TFAM (mitochondrial transcription factor), suggesting a breakdown in the nuclear-mitochondrial communication. Decreased mitophagy-associated proteins p62 and Rheb were observed in aged D2 retina, although p62 was significantly increased in the aged D2 ON. Innovation and Conclusion: The increased reactive oxygen species concomitant with HIF-1α upregulation despite reduced glucose transporters, mis-match of nuclear- and mitochondrial-encoded transcripts, and signs of reduced mitophagy suggest that retinas from D2 mice with chronic intraocular pressure elevation transition to pseudohypoxia without consistent metabolic reprogramming before significant RGC loss.

Subject

glaucoma; oxidative stress; hypoxia; glycolysis; HIF-1α; PGC-1α

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

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ISSN

1557-7716

NEOMED College

NEOMED College of Pharmacy

NEOMED Department

Department of Pharmaceutical Sciences
NEOMED Student Publications

Update Year & Number

May 2021 List

Citation

Jassim AH; Fan Y; Pappenhagen N; Nsiah NY; Inman DM, “Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma.,” NEOMED Bibliography Database, accessed December 8, 2021, https://neomed.omeka.net/items/show/11684.

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