Novel approaches to stimulate regeneration in the retina

Vision loss caused by retinal degeneration remains untreatable, posing a significant medical challenge. Unlike mammals, certain vertebrates like fish and frogs possess a remarkable regenerative ability in their retinas, mediated by Müller glia—specialized support cells that can proliferate and replace lost neurons. In mammals, however, Müller glia fail to regenerate neurons after injury, instead undergoing gliosis and remaining inactive. Our research aims to uncover why mammalian Müller glia lack regenerative capacity and to explore strategies for reactivating their ability to generate neurons. Specifically, we focus on the role of the zinc finger transcription factor Casz1, which influences temporal identity during retinal development. Interestingly, we found that Casz1 expression increases in mouse Müller glia after injury but not in regenerative fish. Using a conditional knock-out (cKO) model, we observed that Müller glia lacking Casz1 in mice begin to transdifferentiate into neuron-like cells, suggesting that Casz1 inhibits regeneration in mammals. Collaborating with Dr. Ryan MacDonald (UCL, UK), we will investigate whether forcing Casz1 expression in zebrafish Müller glia impairs their regenerative abilities. By identifying Casz1 as a key factor in mammalian Müller glia behavior, our work will provide crucial insights for developing therapeutic strategies to restore vision.

Faculty Supervisor:

Michel Cayouette

Student:

Partner:

University College London

Discipline:

Life Sciences

Sector:

Education

University:

McGill University

Program: