» Articles » PMID: 39487142

Massively Parallel Sequencing of Mitochondrial Genome in Primary Open Angle Glaucoma Identifies Somatically Acquired Mitochondrial Mutations in Ocular Tissue

Overview
Journal Sci Rep
Specialty Science
Date 2024 Nov 2
PMID 39487142
Authors
Affiliations
Soon will be listed here.
Abstract

Glaucoma is a sight threatening neurodegenerative condition of the optic nerve head associated with ageing and marked by the loss of retinal ganglion cells. Mitochondrial dysfunction plays a crucial role in the pathogenesis of neurodegeneration in the most prevalent type of glaucoma: primary open angle glaucoma (POAG). All previous mitochondrial genome sequencing studies in POAG analyzed mitochondrial DNA (mtDNA) isolated from peripheral blood leukocytes and have not evaluated cells derived from ocular tissue, which better represent the glaucomatous disease context. In this study, we evaluated mitochondrial genome variation and heteroplasmy using massively parallel sequencing of mtDNA in a cohort of patients with POAG, and in a subset assess the role of somatic mitochondrial genome mutations in disease pathogenesis using paired samples of peripheral blood leukocytes and ocular tissue (Tenon's ocular fibroblasts). An enrichment of potentially pathogenic nonsynonymous mtDNA variants was identified in Tenon's ocular fibroblasts from participants with POAG. The absence of oxidative DNA damage and predominance of transition variants support the concept that errors in mtDNA replication represent the predominant mutation mechanism in Tenon's ocular fibroblasts from patients with POAG. Pathogenic somatic mitochondrial genome mutations were observed in people with POAG. This supports the role of somatic mitochondrial genome variants in the etiology of glaucoma.

Citing Articles

A Comprehensive Review of the Contribution of Mitochondrial DNA Mutations and Dysfunction in Polycystic Ovary Syndrome, Supported by Secondary Database Analysis.

Kobayashi H, Matsubara S, Yoshimoto C, Shigetomi H, Imanaka S Int J Mol Sci. 2025; 26(3).

PMID: 39940939 PMC: 11818232. DOI: 10.3390/ijms26031172.

References
1.
Petriti B, Williams P, Lascaratos G, Chau K, Garway-Heath D . Neuroprotection in Glaucoma: NAD/NADH Redox State as a Potential Biomarker and Therapeutic Target. Cells. 2021; 10(6). PMC: 8226607. DOI: 10.3390/cells10061402. View

2.
Kang I, Chu C, Kaufman B . The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms. FEBS Lett. 2018; 592(5):793-811. PMC: 5851836. DOI: 10.1002/1873-3468.12989. View

3.
Peters D, Bengtsson B, Heijl A . Lifetime risk of blindness in open-angle glaucoma. Am J Ophthalmol. 2013; 156(4):724-30. DOI: 10.1016/j.ajo.2013.05.027. View

4.
Williams P, Harder J, Cardozo B, Foxworth N, John S . Nicotinamide treatment robustly protects from inherited mouse glaucoma. Commun Integr Biol. 2018; 11(1):e1356956. PMC: 5824969. DOI: 10.1080/19420889.2017.1356956. View

5.
Alqawlaq S, Flanagan J, Sivak J . All roads lead to glaucoma: Induced retinal injury cascades contribute to a common neurodegenerative outcome. Exp Eye Res. 2018; 183:88-97. DOI: 10.1016/j.exer.2018.11.005. View