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Association between mitochondrial DNA damage and ocular blood flow in patients with glaucoma
  1. Maki Inoue-Yanagimachi1,
  2. Noriko Himori1,
  3. Kota Sato1,2,
  4. Taiki Kokubun1,
  5. Toshifumi Asano1,
  6. Yukihiro Shiga1,3,
  7. Satoru Tsuda1,
  8. Hiroshi Kunikata1,4,
  9. Toru Nakazawa1,2,3,4,5
  1. 1 Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan
  2. 2 Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Sendai, Japan
  3. 3 Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Japan
  4. 4 Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan
  5. 5 Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  1. Correspondence to Professor Toru Nakazawa, Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; ntoru{at}oph.med.tohoku.ac.jp

Abstract

Background/Aims We determined the relationship between tissue mean blur rate (MT) and mitochondrial dysfunction, represented by the mitochondrial/nuclear DNA (mtDNA/nDNA) ratio. We also investigated the usefulness of these biomarkers.

Methods We assessed ocular blood flow in 123 eyes of 123 patients with open-angle glaucoma (OAG) and 37 control eyes of 37 healthy subjects by measuring MT in the optic nerve head with laser speckle flowgraphy. We measured mtDNA and nDNA with PCR, calculated the mtDNA/nDNA ratio and compared this ratio with MT using Spearman’s rank test. We used multiple regression analysis to further investigate the association between MT and glaucoma in the most severe group.

Results The control and the patients with glaucoma had significant differences in the mtDNA/nDNA ratio, circumpapillary retinal nerve fibre layer thickness and MT. There was no significant relationship between the mtDNA/nDNA ratio and MT in patients with OAG overall or the female patients with OAG, but there was a significant relationship between the mtDNA/nDNA ratio and MT, temporal-MT and superior-MT in male patients with severe OAG (r=−0.46, p=0.03; r=−0.51, p=0.02; r=−0.61, p<0.01, respectively). Furthermore, we found that the mtDNA/nDNA ratio was an independent contributor to temporal-MT and superior-MT in these patients (p<0.01 and p=0.03, respectively).

Conclusion We found that there was a significant relationship between the mtDNA/nDNA ratio and MT in male patients with severe OAG, suggesting that the mtDNA/nDNA ratio may be a new biomarker in glaucoma and may help research on the vulnerability of these patients to mitochondrial dysfunction.

  • glaucoma
  • optic nerve
  • experimental & laboratory

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Footnotes

  • Contributors MI-Y designed the study; contributed to collection, analysis and interpretation of data; drafted the manuscript. NH made substantial contributions to the conception of the study and analysed the data. KS designed the study; provided technical or material support; contributed to critical revisions. TK, TA, YS and ST collected, assembled and analysed the data. HK contributed to critical revisions for important intellectual content. TN contributed to the conception and design of the study and critical revisions for important intellectual content.

  • Funding This work was supported by a JSPS KAKEN Grant-in-Aid for young scientists (NH: 16K20299) and a JST grant from JSPS KAKENHI Grants-in-Aid for scientific research (B) (TN: 26293372).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study followed the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Tohoku University School of Medicine (study 2016-1-708, 2017-1-254, 2016-260).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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