Tadpole, chick models reveal clues to retinal regeneration

Studies in embryonic chicks and frogs indicate that several signaling pathways induce proliferation, differentiation, and apoptosis of retinal progenitor cells and that these pathways cooperate during regeneration, said Katia Del Rio-Tsonis, PhD, associate professor, Department of Zoology, Miami University of Ohio, Oxford.

She conducted retinal regeneration studies in chick and frog models because they have much faster regeneration times than the newt, the animal model of choice for many regeneration experiments. Experiments in Dr. Del Rio-Tsonis? lab showed that fibroblast growth factor (FGF-2) induced regeneration following removal of the retina of stage 43 Xenopus tadpoles. FGF-coated beads and noncoated control beads were implanted after the retina was removed; a complete retina regenerated in tadpole eyes following activation of the FGF pathway.

Investigators determined that several types of retinal cells were present in the regenerated eye and resulted from transdifferentiation of the retinal pigment epithelium tissues. Activation of the MAP kinase pathway by the FGF2 in pigmented epithelium was necessary for the RPE cells to generate the retina.

Dr. Del Rio-Tsonis also studied embryonic day 4 chicks by removing their retinas and injecting retroviruses designed to inhibit or activate the bone morphogenic protein (BMP) or Sonic hedgehog (Shh) pathways. BMP and Shh are regulators for progenitor cell-induced retinal regeneration and can induce regeneration from retinal progenitor cells without exogenous FGF-2. However, endogenous activity is needed for the regeneration process.