NRF‐2 and PGC‐1α signaling regulate epithelial‐mesenchymal transition in mouse model

Abstract

AbstractPurposeEpithelial‐mesenchymal transition (EMT) is estimated to play critical role in the development of advanced age‐related macular degeneration (AMD). Key players associated with EMT were studied in NRF‐2 and PGC‐1α knock‐out mice model resembling dry AMD phenotype.MethodsRetina paraffin sections from NRF‐2 and PGC‐1α knock‐out mice and wild‐type (WT) animals were analyzed for EMT biomarkers by semiquantitative confocal, highly specific and sensitive immunofluorescence method. Retinal pigment epithelium (RPE) cell morphology was analyzed by optical coherent tomography and ultrathin transmission electron microscopy.ResultsSemiquantitative image analysis revealed that collagen 1 is downregulated in knock‐out samples compared to WT animals. Upregulation of key EMT markers such as, vimentin, e/n‐cadherins, snail, fibronectin and slug were detected in the knock‐out mice rather than in WT samples. RPE cells showed morphological transition in the knock‐out animals.ConclusionsDisturbed anti‐oxidant production through nrf‐2 and mitochondrial biogenesis through pgc‐1α seem to regulate emt in the dry amd resembling mouse model.