MicroRNA-184 attenuates hypoxia and oxidative stress-related injury via suppressing apoptosis, DNA damage and angiogenesis in an in vitro age-related macular degeneration model.

Merve Şambel Aykutlu, Hande Güçlü, Zeynep Banu Doğanlar, Ayşe Kardelen Kurtdere, Oğuzhan Doğanlar

Toxicology in vitro : an international journal published in association with BIBRA 2022 Sep

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Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide, particularly in developed countries. Recently, microRNAs (miRs) have become popular research area to develop new treatment options of AMD. However, interaction between hsa-miR-184 and AMD remain largely unexplored. In this study, sub-lethal levels of Deforoxamine Mesylate salt (DFX) and H2O2 were applied to ARPE-19 cells to establish a severe in vitro AMD model, via durable hypoxia and oxidative stress. We found that up-regulation of miR-184 level in AMD can suppress hypoxia-related angiogenic signals through HIF-1α/VEGF/MMPs axis. Also, miR-184 suppressed the hypoxia sensor miR-155 and genes in the EGFR/PI3K/AKT pathway, which is an alternative pathway in angiogenesis. To investigate the mechanism behind this protective effect, we evaluated the impact of miR-184 on retinal apoptosis in a model of AMD. miR-184 inhibited retinal apoptosis by upregulating BCL-2 and downregulating pro-apoptototic BAX, TRAIL, Caspase 3 and 8 signals as well as p53. Taken together, miR-184 attenuates retinal cell damage induced by severe AMD pathologies through suppressing hypoxia, angiogenesis and apoptosis. The safety profile of miR-184 was observed to be similar to Bevacizumab, which is in wide use clinically, but miR-184 was found to provide a more effective therapeutic potential by regulating simultaneously multiple pathologies. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Merve Şambel Aykutlu, Hande Güçlü, Zeynep Banu Doğanlar, Ayşe Kardelen Kurtdere, Oğuzhan Doğanlar. MicroRNA-184 attenuates hypoxia and oxidative stress-related injury via suppressing apoptosis, DNA damage and angiogenesis in an in vitro age-related macular degeneration model. Toxicology in vitro : an international journal published in association with BIBRA. 2022 Sep;83:105413