Aquaporin-1 effect on epithelial-mesenchymal transition in a novel in vitro model of proliferative vitreoretinal diseases

Proliferative vitreoretinal diseases (PVD) are a vision-threatening group of diseases that are often linked to ocular trauma or retinal detachment in the case of proliferative vitreoretinopathy (PVR), and to inflammation or oxidative stress for membranes developing in proliferative diabetic retinopathy (PDR). While many in vivo and in vitro models have been developed to investigate these pathologies, most in vitro models have been abandoned over the years. ARPE-19 cells, a spontaneously arising retinal pigment epithelial cell line, have routinely been used to study the aforementioned diseases but these cells have lost the mature retinal pigment epithelium (RPE) phenotype and lack expression of several RPE genes and proteins' expression.This study aimed to establish a novel in vitro model of proliferative vitreoretinal diseases (PVD) using differentiated ARPE-19 prior to induction of epithelial-mesenchymal transition (EMT) through the addition of TNF-a and TGF-b in the cell culture medium. Furthermore, we studied the effect of induced Aquaporin-1 (AQP1) expression in ARPE-19 cells to evaluate its effect on EMT in this new model, as its expression has been shown to be increased in PVD samples.Transcriptomic profile of these models was then compared to that of human PVD membranes to identify which model is the most representative of human PVD. Our results showed that AQP1 expression had a synergistic effect with TNF-a and TGF-b in enhancing EMT progression of ARPE-19 cells.