Plasticity of adult human retinal pigment epithelial cells

Retinal pigment epithelium (RPE) cell damage underlies many degenerative, dystrophic, and proliferative diseases of the human retina. Primary adult human RPE cells can be used for in vitro modeling of RPE cell behavior under pathological conditions. We demonstrated previously that Wnt7а inhibits adult human RPE cell proliferation, and initiates the spread and polarization of dedifferentiated RPE cells on a plastic surface. Here, we investigated the role of Wnt7a in the regulation of RPE cell plasticity, at cellular and molecular levels. Protein expression and localization were examined by immunofluorescence analysis, while mRNA expression was quantified by real-time PCR. The obtained results showed that Wnt7а influences the expression of a range of neural differentiation markers (nestin, MAP1B, β-tubulin III, synapsin I, 200 kDa and 68 kDa neurofilaments), and increases the expression of various RPE differentiation markers (RPE65, MITF, OTX2, and Pax6). Our findings indicate that Wnt7a exerts a pleiotropic effect on RPE cells in vitro, stimulating redifferentiation (RPE properties), while maintaining neural differentiation indicators. Although this effect was shown to be reversible, Wnt7a may act as a regulator of RPE cell plasticity, and may represent a potential therapeutic target for the prevention of RPE transformation.