In-vivo transdifferentiation of Muller glia to rod photoreceptor or ganglion cell by reprogramming. (A, C) 1st intravitreal injection of AAV2 GFAP β-catenin to induce dedifferentiation of Muller glia to progenitor state. AAV2 GFAP-GFP (green) and AAV2 Rhodopsin-td Tomato (red) reporters were co-injected to mark Muller glia and rod photoreceptors respectively. 2nd intravitreal injection of AAV2 GFAP Otx2-Crx-Nrl to promote Muller glia to adopt rod photoreceptor fate. Rod photoreceptors (red) in ONL are derived from Muller glia. (B, D) Subretinal injection of AAV9 GFAP Math5-Brn3b-GFP to induce Muller glia to adopt ganglion cell fate. Ganglion cells (green) in GCL are derived from Muller glia. GC, ganglion cell; GCL, ganglion cell layer; INL, inner nuclear layer; MG, muller glia; NFL, nerve fiber layer; ONL, outer nuclear layer; RPE, retinal pigment epithelium.