Molecular mechanisms associated with the protective effect of the disaccharide trehalose against oxidative damage in the human retinal pigment epithelial cells

To investigate the protective effect of trehalose and the molecular mechanisms behind its cytoprotection against oxidative damage in cultured human retinal pigment epithelium cells. The human RPE cells were incubated with varying doses of trehalose for 24 hours prior to exposure to a lethal dose of the common cigarette smoke oxidant hydroquinone for 2 hours. The viability of the human RPE cells was then assessed by the trypan blue assay, and the level of oxidative damage was measured using the protein carbonyl ELISA kit. The changes in gene and protein expressions of selected molecular mechanisms involved in oxidative damage in the RPE was quantified using quantitative PCR and Western blot. We found that the human RPE cells exposed to hydroquinone showed significant reduction in the cell viability and increased oxidative stress compared to the control (p < 0.001). Trehalose treatment exerted cytoprotection against the hydroquinone-induced damage and oxidative stress in a dose-dependent manner. The results also showed that the hydroquinone-induced oxidative damage in the human RPE was associated with the dysregulation of the transcriptional and/or proteins expressions of LC3, p62 and Nrf2, Hsp27 and VEGFA. However, the human RPE cells pre-treated with trehalose prevented these changes and protected against the oxidative damage. Trehalose was cytoprotective against oxidative damage by hydroquinone in the human RPE cells. This cytoprotection was associated with the regulation of some cellular antioxidant defence mechanisms altered by hydroquinone. The results warrant further investigation on the therapeutic value of trehalose in alleviating retinal degenerations mediated by oxidative stress. This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.