Retinal pigment epithelial cells and dopamine retinal neurons share the same original precursor cells. It is meaningful to explore the differentiation potential of the established HRPE cell line into retinal neurons or epithelial cell monolayer showing polarized barrier features. To improve the culture environment for the HRPE cells epithelial polarization, Millicell filter inserts were applied, feeding the cells with media of different composition at the apical and basolateral sides. This arrangement allowed the cells to acquire directional polarization, as demonstrated by transepithelial electrical resistance measurements (80±7 W•cm²). This system provided a useful tool for investigating blood-central nervous system barriers functions. Furthermore, we observed that factors such as retinoic acid, epidermal and basic fibroblast growth factors were able to convert HRPE cells into neuron-like cells. However, since such treatment did not actually transform these cells into mature neurons, we investigated the efficacy of other factors in these differentiation-competent cells using light microscopy, ELISA, and RIA assays. We have preliminary noted that a storage of dopamine was induced in differentiation-cocktail treated unlike the untreated cells. Moreover, we characterized the expression and regulation of dopamine-sensitive adenylyl cyclases (AC) specific isoforms, such as AC5 and AC6, using stimulating and/or inhibiting selective compounds on AC activity.