Regeneration of Retinal Neurons in Adult Mice
Increased access to key gene loci in Müller glia enabled mice to generate new retinal neurons after injury
Shutterstock/Nikom nik sunsopa
Damage to the eye's retina through injury or disease is often permanent in adult mammals, since retinal cells cannot regenerate. Most species of fish, on the other hand, can functionally regenerate their retinas. Studies on zebrafish have found that retinal cells originate from Müller glia, glial cells in the retina that undergo de-differentiation into multipotent progenitor cells. From there, the progenitor cells can then differentiate into other retinal cell types.
A team of researchers from the University of Washington has discovered a method that enables adult mice to generate neurons from Müller glia after retinal injury. The new cells behaved like neurons should, forming synapses correctly with host retinal neurons and even responding to light. The results could prove key to eventually developing a novel treatment for eye diseases. The study was published July 26 as a letter in Nature.
Previous work has shown that forced expression of the proneural transcription factor Ascl1 reprograms young mouse Müller glia into neurogenic retinal progenitors. But reduced accessibility to certain regions of DNA prevents regeneration from occurring in adult mice.
To combat this effect, the authors combined overexpression of Ascl1 with a histone deacetylase inhibitor that allowed for accessibility of key gene loci in the Müller glia. These two interventions caused adult mouse MG to generate new inner retinal neurons after injection of a retinal-damaging drug.