New Insights into Dose-Dependent Effects of Curcumin on ARPE-19 Cells

Abstract

Opposing dose-dependent effects of curcumin (Cur) have been documented in Retinal Pigment Epithelium (RPE); therefore, to shed the light on the mechanisms of action is crucial for ophthalmic applications. On this basis we explored new insights about the dose-dependent mechanisms triggered by Cur in human retinal pigment epithelial cells (ARPE-19). Three concentrations (0.01 mM; 0.05 mM; 0.1 mM) of Cur were tested, followed by morphological, molecular, and functional analysis of the cells. Cur 0.01 mM promotes a significant increase in cell proliferation, not affecting cell cycle progression and apoptosis; by contrast, Cur 0.05 mM and 0.1 mM block cellular proliferation and trigger S-phase cell cycle arrest without inducing apoptosis. The observation of neuronal-like morphological changes in Cur 0.05 mM and 0.1 mM were not associated with neuronal differentiation, as observed by the quantification of Neurofilament-200 and by the analysis of voltage-dependent currents by patch clamp. Evaluation of autophagic markers LC3BII and p62 revealed significant modulations, suggesting an important activation of autophagy in ARPE-19 cells treated with Cur 0.05 mM and Cur 0.1 mM; conversely, Cur 0.01 mM did not affect autophagy. Altogether, our findings show new dose-dependent mechanisms of action of Cur that suggest a wide therapeutic application in ocular diseases with different pathogenesis (i.e., proliferative vitreoretinopathy or Age-Related Macular Degeneration).

Small Extracellular Vesicles and Oxidative Pathophysiological Mechanisms in Retinal Degenerative Diseases

“…These miRNAs contained in sEVs have in fact been proposed as mediators of homeostasis [89], which, we believe, they might be. In this report, photo-oxidative conditions induced a decrease in the amount, but not in their size, of sEVs production (contrary to what has been reported by others under photo-oxidative stimuli [73]), obtained from whole mouse retina homogenates. Other publications showed, as mentioned above, that other oxidative stimuli, in fact, increase the amount of sEVs production [22,35,36], it might well be that this discrepancy resides in the sEVs collecting procedure.…”

“…This effect was accompanied by a decrease in the total number of sEVs and the VEGFR2-positive sEVs released from ARPE-19 cells [36]. Interestingly, high doses of the antioxidant curcumin have shown activation of autophagy [73]; these authors did not evaluate sEV release, though their results allow the speculation that, under these conditions, an increase in sEVs could certainly be expected.…”

Machine Learning Elucidates Design Features of Plasmid DNA Lipid Nanoparticles for Cell Type-Preferential Transfection

“…The two exceptions were N2a and ARPE-19 cells, which were the most highly correlated cell lines with a Spearman's rank correlation coefficient of 0.71. We attributed the high correlation to the shared neuronal origins of ARPE-19 and N2a cells 31,32 . Our results suggest that it may be possible to exploit interactions between LNP design features and certain cellular features of the target cell type to develop tailored LNPs for cell type-preferential transfection through modulation of the formulation compositions and helper lipid identity.…”