Strategies for Müller glia reprogramming through electroporation

The vertebrate retina is composed of six neuronal types and a major glial type, the Müller glia (MG). This glial type has endogenous regenerative potential in teleost fish, but in mammals this is very limited. Several research groups have sought to reprogram MG to activate their neurogenic capacity and generate new neurons as a regenerative strategy for ocular neuropathies that lead to irreversible visual loss, such as glaucoma. Previously, our group demonstrated that Klf4 overexpression in late retinal progenitors, which have transcriptional and epigenetic profiles similar to MG, promotes the reacquisition of the potential to generate induced retinal ganglion cells (iRGCs), which are normally generated in the early embryonic period (Development 146: dev176586, 2019). Our hypothesis is that the MG can be reprogrammed with Klf4 to generate iRGCs.