Mechanisms of Transdifferentiation and Regeneration

Hundreds of millions of people across the world suffer from severely impaired vision and as the population of the world grows older, this problem will become more severe. One avenue of therapy for these patients may be to induce healthy cells of the eye to regenerate cells that may be lost or damaged due to disease. The research in this dissertation focuses on regeneration via a process called transdifferentiation, wherein differentiated cells undergo dedifferentiation, proliferate and then redifferentiate to replace lost or damaged cells. Very few animals can regenerate ocular tissues and two such animals have been used in my research. The adult newt has been used to study the process of lens regeneration whereas the embryonic chick has been used to study retina regeneration. Our studies using the newt have helped us identify a novel non-immunological role for complement components C3 and C5. Our studies show that these molecules are expressed during a variety of regenerative tissues and our results suggest that these molecules might convey positional information during regeneration. We have also studied the role of the transcription factor Pax-6 during lens regeneration and show that it is required for the proliferation of cells and differentiation of lens fibers. We have established the chick as a good model system to study regeneration. We have also shown that the chick is not only a good model to study transdifferentiation but also to study the activation of progenitor cells. The work described in this dissertation also dissects the Fibroblast Growth Factor signaling cascade that is involved during transdifferentiation and also examines the roles of transcription factors such as Pax-6 and Microphthalmia during retina regeneration.