Protective effects of resveratrol on the ethanol‐induced disruption of retinogenesis in pluripotent stem cell‐derived organoids

Abstract

Prenatal alcohol exposure‐induced fetal alcohol syndrome (FAS) can lead to serious maldevelopment in many organ systems, including the eyes. In the present study, the effects of alcohol exposure on early development of the human retina and the therapeutic effects of resveratrol on alcohol‐induced neural retinal damage were observed for the first time in an in vitro retinal organoid model. We report that the number of proliferating and apoptotic cells decreased and increased, respectively, following ethanol treatment. In addition, the number of PAX6 + cells and migrating TUJ1 + cells decreased after ethanol exposure. However, pretreatment with resveratrol prevented all of these negative effects. Using RNA sequencing and immunofluorescence, we identified activation of the PI3K‐AKT signalling pathway as the possible mechanism through which resveratrol protects the retina from alcohol‐induced damage. These results suggest that while ethanol exposure can restrict the growth of the human retina and impede the development of specific retinal cells, pretreatment with resveratrol may be a feasible method for preventing these effects.

Effect of Resveratrol on PI3K/Akt/GSK-3β Pathway and Metalloproteases in Differentiated and Aβ-Induced Alzheimer's Model Neuroblastoma Cells

“…A recent study has shown that resveratrol can play a protective role in the neural retina from alcohol exposure by activating the PI3K/AKT signaling pathway. Additionally, it was detected, that the expression levels of RELN, FGFR2, MET, and PIK3AP1 were upregulated with the treatment of RES in comparisons (Li et al 2023). In our study, we found that RELN mRNA levels increased under resveratrol treatment.…”