Melatonin Type 2 Receptor Activation Regulates Blue Light Exposure-Induced Mouse Corneal Epithelial Damage by Modulating Impaired Autophagy and Apoptosis

Int J Mol Sci. 2022 Sep 26;23(19):11341. doi: 10.3390/ijms231911341.

Abstract

The MT1/2 receptors, members of the melatonin receptor, belong to G protein-coupled receptors and mainly regulate circadian rhythms and sleep in the brain. Previous studies have shown that in many other cells and tissues, such as HEK293T cells and the retina, MT1/2 receptors can be involved in mitochondrial homeostasis, antioxidant, and anti-inflammatory responses. In our study, we aimed to investigate the effects of blue light (BL) exposure on the expression of melatonin and its receptors in the mouse cornea and to evaluate their functional role in corneal epithelial damage. After exposing 8-week-old C57BL/6 mice to BL at 25 and 100 J/cm2 twice a day for 14 days, a significant increase in the expression of 4-HNE and MT2 was observed in the cornea. MT2 antagonist-treated mice exposed to BL showed an increased expression of p62 and decreased expression of BAX and cleaved caspase 3 compared with mice exposed only to BL. In addition, MT2 antagonist-treated mice showed more enhanced MDA and corneal damage. In conclusion, BL exposure can induce MT2 expression in the mouse cornea. MT2 activation can modulate impaired autophagy and apoptosis by increasing the expression of BAX, an apoptosis activator, thereby regulating the progression of corneal epithelial damage induced by BL exposure.

Keywords: apoptosis; autophagy; blue light; corneal damage; melatonin type 2 receptor.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Antioxidants
  • Apoptosis
  • Autophagy
  • Caspase 3
  • Cornea / metabolism
  • Corneal Injuries*
  • HEK293 Cells
  • Humans
  • Melatonin* / pharmacology
  • Melatonin* / physiology
  • Mice
  • Mice, Inbred C57BL
  • Receptor, Melatonin, MT1 / metabolism
  • Receptor, Melatonin, MT2 / metabolism
  • bcl-2-Associated X Protein / genetics

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • bcl-2-Associated X Protein
  • Caspase 3
  • Melatonin