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27 reviewsIndividuals with retinal degenerative diseases struggle to restore vision due tothe inability to regenerate retinal cells. Unlike cold-blooded vertebrates,mammals lack Müller glia (MG)-mediated retinal regeneration, indicating thelimited regenerative capacity of mammalian MG. Here, we identify prosperorelated homeobox 1 (Prox1) as a key factor restricting this process. Prox1accumulates in MG of degenerating human and mouse retinas but not inregenerating zebrafish. In mice, Prox1 in MG originates from neighboringretinal neurons via intercellular transfer. Blocking this transfer enables MGreprogramming into retinal progenitor cells in injured mouse retinas. Moreover, adeno-associated viral delivery of an anti-Prox1 antibody, whichsequesters extracellular Prox1, promotes retinal neuron regeneration anddelays vision loss in a retinitis pigmentosa model. These findings establishProx1 as a barrier to MG-mediated regeneration and highlight anti-Prox1therapy as a promising strategy for restoring retinal regeneration in mammals