Melatonin mitigates disrupted circadian rhythms, lowers intraocular pressure, and improves retinal ganglion cells function in glaucoma

Denis Gubin, Vladimir Neroev, Tatyana Malishevskaya, Germaine Cornelissen, Sergei Y. Astakhov, Sergey Kolomeichuk, Natalya Yuzhakova, Yana Kabitskaya, Dietmar Weinert

Research output: Contribution to journalArticlepeer-review

Abstract

Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin is a promising substance to ameliorate glaucoma-associated compromised circadian rhythms, sleep, mood, and retinal cells function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long-term (daily at 10:30 pm for 90 days) oral melatonin administration on systemic (Tb) and local to the organ of vision (IOP) circadian rhythms, pattern electroretinogram (PERG), sleep, and mood, depending on glaucoma stage in patients diagnosed with stable or advanced primary open-angle glaucoma. In a laboratory study in 15 of them, 24-hour records of salivary melatonin were obtained and MTNR1B receptor gene polymorphism was assessed. Melatonin increased the stability of the Tb circadian rhythm by improving its phase alignment and alignment with IOP. Melatonin time-dependently decreased IOP and IOP standard deviation (SD). IOP 24-hour mean and IOP SD decreases were more pronounced in individuals with the higher initial 24-hour IOP mean. Melatonin improved RGCs function in advanced glaucoma; N95 amplitude increase correlated positively with RGCs loss. The beneficial effects of melatonin on sleep and mood were greater in advanced glaucoma. Finally, delayed salivary melatonin and Tb phases were observed in MTNR1B G-allele carriers with advanced glaucoma. Combined, these results provide evidence for melatonin efficiency in restoring disrupted circadian rhythms in glaucoma with different effects of melatonin on systemic vs. local circadian rhythms, indicating that a personalized strategy of melatonin administration may further refine its treatment benefits.

Original languageEnglish (US)
Article numbere12730
JournalJournal of Pineal Research
Volume70
Issue number4
DOIs
StatePublished - May 2021

Bibliographical note

Funding Information:
The study was supported by the Russian Foundation for Basic Research (Grant No. 19‐015‐00329), Minisrty of Education and Science of the Russian Federation (Grant No. 0218‐2019‐0077), and by Government of Tyumen District, Decree of 20.11.2020 No. 928‐rp. The funding organization had no role in the design or conduct of this research. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • MTNR1B
  • circadian disruption
  • circadian rhythm
  • electroretinogram
  • gene polymorphism
  • glaucoma
  • intraocular pressure
  • melatonin
  • mood
  • sleep
  • temperature

PubMed: MeSH publication types

  • Journal Article

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