Common Mechanisms of Retinal Regeneration in the Larval Frog and Embryonic Chick

Amphibians and embryonic chicks possess the ability to regenerate retinal neurons by the transdifferentiation of pigment epithelium into neuronal progenitors. Recent studies have begun to identify the molecular factors involved in this process. Laminin (a component of the extracellular matrix) has been shown to be important in the process of retinal regeneration in the larval frog both in vitro and in vivo and basic fibroblast growth factor (bFGF) stimulates the same process in chicks in vivo. To determine the mechanisms by which these factors induce retinal regeneration we studied their effects on cultured chick pigment epithelium cells. bFGF was added to enzymically dissociated chick embryo pigment epithelial cells plated at several different densities on various substrates including laminin. We found that bFGF stimulated proliferation but although the cells lost pigmentation and demonstrated distinct morphological changes, no definitive transdifferentiation could be demonstrated using several neuron-specific antibodies as markers. When the pigment epithelium was cultured as aggregates on a shaker device which prevented flattening and spreading on the substrate a large number of retinal progenitor cells were generated from the pigment epithelium treated with bFGF. The ability of chick pigment epithelium to undergo transdifferentiation thus appears to be dependent on the physical configuration of the cells.