A Method to Reprogram Glial Cells into Cone Photoreceptors

A method using an endogenous source of mammalian stem cell, the Müller glia, to regenerate photoreceptor cells directly within the retina. Ex vivo co-expression experiments have shown that ZFTF1 and ZFTF4 factors can reprogram Müller glial cells into immature cone-like cells in mouse renal explants. The co-expression (ZFTF1 and ZFTF4) induced clear morphological changes in 59% of the Müller glial cells. The co-expression also induced a migration of the majority of the Müller glial cells (61.1%) toward the apical side of the retina, where cone photoreceptors are usually located. Immunoflorescence studies have shown a down regulation of Müller specific gene expressions (Lhx2 and Sox2) in the morphologically reprogrammed cells. Immunoflorescence studies have also shown that the majority of the morphologically reprogrammed cells (79.3%) expressed RxRg, an early cone photoreceptor marker. In vitro co-expression experiments have showed that ZFTF1 and ZFTF4 factors can reprogram Müller glial cells into cones expressing mature markers such as s-opsin. Preliminary mouse in vivo experiments showed that AVV-ZFTF4 (adeno-associated viral vector) could infect adult retinas and induce expression of ZFTF4 in a large proportion of Müller glia. These in vivo experiments also showed ZFTF4 induced expression of RxRg in these cells. Benoît Doré benoit.dore@axelys.ca (514) 340 8521