Hippo pathway inhibition restores visual function in blind mice via Müller glia-derived photoreceptor regeneration

Extending our previous finding that targeting the core Hippo effector YAP drives limited Müller glia (MG)-to-inner retinal neuron transdifferentiation yet induced marked, transient MG migration toward the outer retina, even in an inner retinal injury model. These results indicate that YAP holds high potential to instruct photoreceptor fate from endogenous MG.

Here, we show that Hippo pathway acts as a master regulator governing MG trans-differentiation into photoreceptors. Genetic and pharmacological modulation of YAP promotes MG proliferation and drives their commitment to a photoreceptor lineage in a mouse model of outer nuclear layer injury.A single intravitreal injection of TDI‑011536 delivered via GelMA‑encapsulated mesoporous silica nanoparticles achieves substantial photoreceptor regeneration and restores visual function in blind mice, without systemic toxicity.