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VOLUME 16 , ISSUE 3 ( September-December, 2022 ) > List of Articles

ORIGINAL RESEARCH

Mitochondrial Genome Alterations, Cytochrome C Oxidase Activity, and Oxidative Stress: Implications in Primary Open-angle Glaucoma

Kuldeep Mohanty, Swetasmita Mishra, Rima Dada, Tanuj Dada

Keywords : Case-control study, Cytochrome C oxidase, Mitochondrial genome alterations, Oxidative stress, Primary open-angle glaucoma

Citation Information : Mohanty K, Mishra S, Dada R, Dada T. Mitochondrial Genome Alterations, Cytochrome C Oxidase Activity, and Oxidative Stress: Implications in Primary Open-angle Glaucoma. J Curr Glaucoma Pract 2022; 16 (3):158-165.

DOI: 10.5005/jp-journals-10078-1376

License: CC BY-NC 4.0

Published Online: 23-01-2023

Copyright Statement:  Copyright © 2022; The Author(s).


Abstract

Aim: To evaluate mitochondrial genome alterations, cytochrome C oxidase (COX) activity, and oxidative stress in primary open-angle glaucoma (POAG). Methodology: Whole mitochondrial genome was screened in 75 POAG cases and 105 controls by polymerase chain reaction (PCR) sequencing. COX activity was measured from peripheral blood mononuclear cells (PBMCs). A protein modeling study was done to evaluate the impact of G222E variant on protein function. Levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-isoprostane (8-IP), and total antioxidant capacity (TAC) were also measured. Results: A total of 156 and 79 mitochondrial nucleotide variations were found in the cohort of 75 POAG patients and 105 controls, respectively. Ninety-four (60.26%) variations spanned the coding region, and 62 (39.74%) variations spanned noncoding regions (D-loop, 12SrRNA, and 16SrRNA) of mitochondrial genome in POAG patients. Out of 94 nucleotide changes in coding region, 68 (72.34%) were synonymous changes, 23 (24.46%) non-synonymous, and three (3.19%) were found in the region coding for transfer ribonucleic acid (tRNA). Three changes (p.E192K in ND1, p.L128Q in ND2, and p.G222E in COX2) were found to be pathogenic. Twenty-four (32.0%) patients were positive for either of these pathogenic mitochondrial deoxyribonucleic acid (mtDNA) nucleotide changes. Majority of cases (18.7%) had pathogenic mutation in COX2 gene. Patients who harbored pathogenic mtDNA change in COX2 gene had significantly lower levels of COX activity (p < 0.0001) and TAC (p = 0.004), and higher levels of 8-IP (p = 0.01) as compared to patients who did not harbor this mtDNA. G222E changed the electrostatic potential and adversely impacted protein function of COX2 by affecting nonpolar interactions with neighboring subunits. Conclusion: Pathogenic mtDNA mutations were present in POAG patients, which were associated with reduced COX activity and increased levels of oxidative stress. Clinical significance: POAG patients should be evaluated for mitochondrial mutations and oxidative stress and may be managed accordingly with antioxidant therapies.

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