Melatonin inhibits NaIO-induced ARPE-19 cell apoptosis via suppression of HIF-1α/BNIP3-LC3B/mitophagy signaling.

BACKGROUND

Age-related macular degeneration (AMD) leads to gradual central vision loss and eventual irreversible blindness. Melatonin, an endogenous hormone, exhibits anti-inflammatory and antitumor effects; however, the role it plays in AMD remains unclear. Herein, we investigated the anti-AMD molecular mechanism of melatonin after sodium iodate (NaIO3) treatment of ARPE-19 cells in vitro and in animal models with the goal of improving the therapeutic effect.

RESULTS

The in vitro results showed that melatonin protected against NaIO-induced cell viability decline, mitochondrial dysfunction and apoptosis in ARPE-19 cells, and melatonin also alleviated NaIO-induced reactive oxygen species (ROS) production, mitochondrial dysfunction and mitophagy activation. Melatonin reduced NaIO-induced mitophagy activation through HIF-1α-targeted BNIP3/LC3B transcription, whereas ROS inhibition realized with N-acetylcysteine (NAC, a ROS inhibitor) combined with melatonin reduced the effect of NaIO on mitophagy. An animal model of AMD was established to confirm the in vitro data. Mouse tail vein injection of NaIO and melatonin was associated with enhanced repair of retinal layers within 7 days, as observed by optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining. A reduction in BNIP3 and HIF-1α levels, as determined by immunohistochemistry (IHC) assay, was also observed.

CONCLUSIONS

These results indicate that melatonin attenuated NaIO-induced mitophagy of ARPE-19 cells via reduction in ROS-mediated HIF-1α targeted BNIP3/LC3B signaling in vitro and in vivo. Melatonin may be a potential therapeutic drug in the treatment of AMD.