Low mitochondrial DNA copy number in buffy coat DNA of primary open-angle glaucoma patients.

Autor: Vallbona-Garcia A; University Eye Clinic Maastricht, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands. Electronic address: a.vallbonagarcia@maastrichtuniversity.nl., Hamers IHJ; Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands., van Tienen FHJ; Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands., Ochoteco-Asensio J; Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands., Berendschot TTJM; University Eye Clinic Maastricht, Maastricht University Medical Center+, Maastricht, the Netherlands., de Coo IFM; Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands., Benedikter BJ; University Eye Clinic Maastricht, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands., Webers CAB; University Eye Clinic Maastricht, Maastricht University Medical Center+, Maastricht, the Netherlands., Smeets HJM; Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands., Gorgels TGMF; University Eye Clinic Maastricht, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2023 Jul; Vol. 232, pp. 109500. Date of Electronic Publication: 2023 May 11.
DOI: 10.1016/j.exer.2023.109500
Abstrakt: Primary open-angle glaucoma (POAG) is characterized by optic nerve degeneration and irreversible loss of retinal ganglion cells (RGCs). The pathophysiology is not fully understood. Since RGCs have a high energy demand, suboptimal mitochondrial function may put the survival of these neurons at risk. In the present study, we explored whether mtDNA copy number or mtDNA deletions could reveal a mitochondrial component in POAG pathophysiology. Buffy coat DNA was isolated from EDTA blood of age- and sex-matched study groups, namely POAG patients with high intraocular pressure (IOP) at diagnosis (high tension glaucoma: HTG; n = 97), normal tension glaucoma patients (NTG, n = 37), ocular hypertensive controls (n = 9), and cataract controls (without glaucoma; n = 32), all without remarkable comorbidities. The number of mtDNA copies was assessed through qPCR quantification of the mitochondrial D-loop and nuclear B2M gene. Presence of the common 4977 base pair mtDNA deletion was assessed by a highly sensitive breakpoint PCR. Analysis showed that HTG patients had a lower number of mtDNA copies per nuclear DNA than NTG patients (p-value <0.01, Dunn test) and controls (p-value <0.001, Dunn test). The common 4977 base pair mtDNA deletion was not detected in any of the participants. A lower mtDNA copy number in blood of HTG patients suggests a role for a genetically defined, deficient mtDNA replication in the pathology of HTG. This may cause a low number of mtDNA copies in RGCs, which together with aging and high IOP, may lead to mitochondrial dysfunction, and contribute to glaucoma pathology.
Competing Interests: Declaration of competing interest The authors declare no relevant conflicts of interest.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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