Immunoperoxidase and molecular genetic analysis showed that retinal pigment epithelial cells from adult human eye undergo morphogenetic changes in vitro. They lose expression of tissue-specific protein RPE65 and start to express stem cell markers: Oct4 (POU5F1), Nanog, Prox1, Musashi 1, and Pax6, which indicates their differentiation. Expression of Musashi 1 and Pax6 attest to neural differentiation, which is also confirmed by the expression of βIII-tubulin, a neuroblast marker, and markers of differentiated neuronal cells, tyrosine hydroxylase and neurofilament proteins. These findings attest to the capacity of retinal pigment epithelium from adult human eye to transdifferentiation into neural lineage cells, which makes them an interesting object for cell therapy in neurodegeneration.

Phenotypic plasticity of retinal pigment epithelial cells from adult human eye was studied by immunohistochemical methods under different culturing conditions. It was found that retinal pigment epithelium in adult human eye is a heterogeneous population of cells demonstrating different behavior in vitro. Some cells retain epithelial morphology for a long time in culture, while others are rapidly transformed into fibroblast-like cells and synthesize proteins typical of proneural, neural, glial, and photoreceptor cells. However, irrespective of initial morphological features differentiation of retinal pigment cells can be modulated by varying culturing conditions.

Multipotent characteristics of human fetal (9-11.5 weeks) pigmented epithelial retinal cells and capacity to transdifferentiation in neuronal direction were studied in vitro under different culturing conditions. The cultures were analyzed using a wide spectrum of antibodies. It was found that pigmented epithelium of human eye is a heterogeneous cell population with three subtypes differing by adhesion characteristics, migration, transdifferentiation potential, and reaction to microenvironmental factors. Subtype 1 cells steadily retain their epithelial characteristics, subtype 2 cells change their morphotype and produce neuroblast and photoreceptor cell proteins, and subtype 3 cells form free floating spheres and are capable to multipotent differentiation.

Expression of transforming growth factor-β2 was detected by PCR in the vitreous body, lens, retina, and ciliary-iris complex of human eye at early stages of fetal development. Immunochemical assay of the corresponding protein in eye tissues revealed a correlation between the localization of transforming growth factor-β2 and the development of intraocular hyaloid vascular network, its regression, formation of the vitreous body, and development of definite retinal vessels.

We compared the expression of Sox2, Oct4, Nanog, Pax6, Prox1 genes associated with plasticity of neural stem and progenitor cells during human neocortex and retina development and in cell cultures. At the analyzed stages of neurogenesis, Pax6 gene is expressed in the neocortex and retina at constant levels, the expression is by one order of magnitude higher in the retina. The dynamics of Sox2 and Pax6 expression in the neocortex was similar. The expression of Oct4 and Nanog genes during neurogenesis in the neocortex and human fetal retina reflects the existence of a high-plasticity cell pool. The dynamics of βIII-tubulin expression indicates that the retina develops more rapidly than the neocortex. Our experiments showed that genetically determined cell potencies typical of native cells are realized in primary cultures without specific stimulation.