HOW TO DRIVE EMBRYONIC STEM CELLS TOWARD A RETINAL FATE: ROLE OF EYE SPECIFIC TRANSCRIPTION FACTORS

Neurodegenerative diseases like retinitis pigmentosa (RP) may result from the malfunctioning of many genes. Setting up the experimental protocols for gene therapy of each of these genes poses many difficulties. This is the reason why several researchers hope to be able to replace the degenerated nervous retinal cells in the various forms of RP by stem cell transplant. By now, however, none of the attempts to transform stem cells in fully functional retinal cells seems to have been completely successful. Our aim is to identify the right combination of genes able to transform stem cells in retinal ones, bypassing normal embryonic development processes, and replace the degenerated cells in RP. To do this, we need to investigate the mechanisms by which retinal cells develop in a normal embryo, then to transfer this knowledge to in vitro cultured stem cells. These studies require the use of animal models to study the in vivo condition. We plan to utilize simple vertebrates such as amphibians for the following reasons: the majority of the genes and their function are very similar in most vertebrates; studies on amphibian embryos are faster and simpler than on mammals; most genes that drive retinal cell development have been recently isolated and investigated in amphibians. Moreover, the data gathered on amphibians will be easily applied to the manipulation of mouse stem cells. The latter is the final aim of our research. The fall-back of this basic studies will contribute to the development of innovative strategies in human stem cell therapy of RP.