Melatonin antagonizes oxidative stress-induced mitochondrial dysfunction in retinal pigmented epithelium cells via melatonin receptor 1 (MT1)

Abstract

High energy-consumption in retinal pigmented epithelium (RPE) cells poses oxidative stress (OS) and contributes to mitochondrial dysfunction (MD) for retinal degeneration-associated diseases. In the present study, we evaluated the protective role of Melatonin, a natural antioxidant, against the hydrogen peroxide (H 2 O 2)-induced damage to RPE cells. The cellular viability, apoptosis, the expression of apoptosis-associated proteins and mitochondrial function were examined in the retinal ARPE-19 cells, post the treatment with H 2 O 2 or (and) with Melatonin. The regulation by Melatonin receptor 1 (MT1) on the Melatonin-mediated protection was also examined via MT1 knockdown with siRNA. Results demonstrated that Melatonin significantly ameliorated cell viability reduction, reduced apoptosis and downregulated the apoptosis-associated proteins in H 2 O 2-treated ARPE-19 cells. The H 2 O 2-induced mitochondrial dysfunction was also significantly blocked by the Melatonin treatment, presenting as a reduced accumulation of reactive oxygen species (ROS) and mitochondrial superoxide and an ameliorated reduction of mitochondrial membrane potential (MMP). In addition, the knockdown of MT1 with MT1-specific siR-NA inhibited the Melatonin-mediated protection against OS damage in ARPE-19 cells. In summary, we confirmed the protective role of Melatonin against H 2 O 2-induced mitochondrial dysfunction in RPE cells. MT1 knockdown blocked such protective role of Melatonin. It is implied that Melatonin exerts a protective role against oxidative stress via Melatonin-MT1 signaling in RPE cells.

Melatonin protects the retina from experimental nonexudative age‐related macular degeneration in mice

“…In addition, melatonin has shown to rescue mitochondria functionality by reducing oxidative stress and increasing mitochondria biogenesis in diabetic myocardial ischaemia/reperfusion damage . There are reports showing melatonin exerts its protective effects against oxidative stress through MT1 and/or MT2 receptors; however, receptor‐independent antioxidant effects of melatonin have also been described . At present, we cannot ascertain whether the protective effect of melatonin against NE‐AMD involves receptor‐dependent or receptor‐independent mechanisms, an issue that will be analysed in the near future.…”

Light-Induced Stress as a Primary Evolutionary Driver of Eye Origins

“…Melatonin receptors regulate intracellular adenylyl cyclase in response to local melatonin concentrations, and are integral in many ROS and UV damage mitigating pathways like melanin production. (Fischer et al 2008;Galano et al 2011;Yan et al 2018) . Retinoic Acid (RA) can also be used as a sensor for UV stress, but unlike melatonin, retinoic acid fluctuations are more specifically tied to UV exposure, dropping more than fifty percent in the presence of UV light (Tolleson et al 2005) .…”

Light-Induced Stress as a Primary Evolutionary Driver of Eye Origins

“…Melatonin acts as a powerful scavenger of ROS but it is quickly broken down by both ROS and UV light, leading to intracellular melatonin concentrations that closely track oxidative and UV stress levels (Xu et al 2009). Melatonin receptors regulate intracellular adenylyl cyclase in response to local melatonin concentrations, and are integral in many ROS and UV damage mitigating pathways like melanin production (Fischer et al 2008;Galano et al 2011;Yan et al 2018). Second, retinoic acid has clear advantages for mediating photo-stress and is used by existing photostress pathways.…”