System behind retina regeneration found

A team of scientists from the Baylor College of Medicine Cardiovascular Research Institute and the Texas Heart Institute found that while the mammalian retina does not spontaneously regenerate, it possesses regenerative properties that are kept dormant by a cellular mechanism known as the Hippo pathway.“However, other animals such as zebrafish can reverse blindness thanks to specialised cells in the retina called Müller glial cells. When the retina is damaged, Müller glial cells proliferate and differentiate into the lost retinal neurons, effectively replacing injured cells with fully functional ones, study lead author Dr. Ross A. Poché, assistant professor of molecular physiology and biophysics at Baylor, said.While Müller glial cells in injured mammalian retinas do not restore vision as it does in zebrafish, other researchers have studied that when the mammalian retina is injured, a small subset of Müller glial cells takes the first steps needed to begin the regeneration cycle.“But this attpt to proliferate is transient; after acquiring some of the cell markers the cells shut off,” Poché explained.“These observations suggested that the mechanism that drives cell repair in zebrafish also might be present in mammals, but it is actively suppressed. For years, the suppressing mechanism was unknown.”To identify and study the suppressing mechanism, Poché’s group teamed up with co-author Dr James Martin, professor of molecular physiology and biophysics, Vivian L. Smith Chair in Regenerative Medicine at Baylor College of Medicine.The research team focused on the Hippo pathway’s network of molecular events that contributes to organ growth during development. Martin’s lab previously found that the Hippo pathway acts as a ‘break’ on cardiomyocyte proliferation by inhibiting the activity of another pathway called YAP.Creating a malfunctioning Hippo pathway resulted in modest cell proliferation and when the researchers genetically engineered Müller glial cells to carry a version of YAP that is impervious to the inhibitory influence of Hippo, the cells showed major proliferation. More importantly, a small subset of these Müller glia-derived progenitor cells showed signs of spontaneous differentiation into new retinal neurons.“Our next step is to develop a strategy to guide proliferating Müller glial cells into differentiation pathways leading to retinal cells capable of restoring vision,” Poche said.The findings were published in the journal Cell Reports.