The Effect of Basic Fibroblast Growth Factor on Signaling Pathways in Adult Human Retinal Pigment Epithelial Cells

Abstract

Retinal pigment epithelium (RPE) plays a key role in the development of many eye diseases characterized by visual impairment and even blindness. The use of cell cultures to model changes in RPE makes it possible to study stimulating factors and signaling pathways that coordinate the cellular and molecular mechanisms of intercellular interactions under pathological conditions. In addition, it is possible to identify targets and develop a specific therapy to eliminate pathological changes in the retina. Based on the results of previously obtained experimental data on decreased differentiation of RPE cells in the direction of the neuroepithelium after a single exposure to basic fibroblast growth factor (bFGF), research in this area was continued and changes in Wnt-, BMP-, and Notch-signaling pathways were examined. It is necessary for a deeper understanding of the mechanisms that decrease the level of differentiation of RPE cells. It was found that the addition of bFGF to culture decreased immunocytochemical staining for β-catenin; increased staining for Wnt7a, BMP2, and BMP7; and altered localization of stained BMP4. In addition, quantitative real-time PCR of RPE cells treated with bFGF revealed enhanced expression of mRNA of BMP2, a decreased expression of mRNA genes, such as CTNNB1, BMP4, and BMPR2, as well as mRNA of Notch-signaling genes, such as JAG1, NOTCH1, HES1, and HEY1. Analysis of the data indicates inactivation of the Wnt/β-catenin and Notch-signaling pathways, activation of the noncanonical Wnt/PCP signaling pathway, and modulating of BMP-signaling with a decrease in the level of differentiation of adult RPE cells after their a single (short-term) exposure to bFGF. Thus, the results obtained clarify the mechanisms of dedifferentiation of RPE cells under the influence of bFGF.