Abstract
Purpose: :
The Pax6 gene plays important roles in morphogenesis of the eye. The Pax6 gene and its homologue could form ectopic eyes by targeted expression in Drosophila and Xenopus. Thus, this gene is a master gene for the eye morphogenesis at least in these animals. In the early development of the vertebrate eye, Pax6 is required for instruction of multipotential progenitor cells of the neural retina (NR). Primitive retinal pigment epithelial (RPE) cells are able to switch their phenotype and differentiate into NR under exogenous intervention, including treatment with fibroblast growth factors (FGFs), and surgical removal of endogenous NR. However, the molecular basis of phenotypic switching is still controversial.
Methods: :
We transduced the human Pax6 gene into avian RPE cells in vivo by electroporation and evaluated it by in situ hybridization and immunohistochemistry. In vitro, Pax6 expression by FGF stimulus was analyzed by CAT assay.
Results: :
Pax6-mediated transdifferentiation can be induced even at later stages of development. Both in vivo and in vitro studies show that the Pax6 lies downstream of FGF signaling, highlighting the central roles of Pax6 in NR transdifferentiation.
Conclusions: :
Our results provide an evidence of retinogenic potential of nearly mature RPE and a cue for new therapeutic approaches to regenerate functional NR in patients with a visual loss.
Keywords: retina • retinal pigment epithelium • gene transfer/gene therapy