Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron Regeneration

Müller glia exhibit a remarkable regenerative capacity in zebrafish through spontaneous reprogramming post-injury but remain limited in mammals. This review highlights the key mechanisms underlying Müller glia reprogramming, including gene regulatory networks, cytokine signaling, signal transduction...

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Main Authors: Yuyan Zhou, Song Qin, Haixiang Wu
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Neuroglia
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Online Access:https://www.mdpi.com/2571-6980/6/2/20
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author Yuyan Zhou
Song Qin
Haixiang Wu
author_facet Yuyan Zhou
Song Qin
Haixiang Wu
author_sort Yuyan Zhou
collection DOAJ
description Müller glia exhibit a remarkable regenerative capacity in zebrafish through spontaneous reprogramming post-injury but remain limited in mammals. This review highlights the key mechanisms underlying Müller glia reprogramming, including gene regulatory networks, cytokine signaling, signal transduction pathways, epigenetic modifications, and transcriptional regulation. Cross-species analyses have uncovered conserved gene networks that suppress neurogenesis in mammals, while injury-induced transcriptional profiles reveal divergent regenerative strategies. Combinatorial approaches may enhance the reprogramming of mammalian Müller glia into functional neurons. Nevertheless, significant challenges remain, such as variability in the efficacy of direct reprogramming methods and the limited regeneration of cone photoreceptors, even in regenerative species. We conclude that targeting epigenetic barriers and species-specific regulatory pathways offers promising avenues for clinical translation in retinal disorders such as glaucoma and retinitis pigmentosa. Moving forward, research efforts should prioritize the functional integration of regenerated neurons and the development of standardized methodologies to accelerate therapeutic advancements.
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spelling doaj-art-d8384d5df41b40bab67c7075fcd56ac32025-08-20T03:16:24ZengMDPI AGNeuroglia2571-69802025-05-01622010.3390/neuroglia6020020Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron RegenerationYuyan Zhou0Song Qin1Haixiang Wu2Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, ChinaDepartment of Anatomy, Histology and Embryology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, ChinaDepartment of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, ChinaMüller glia exhibit a remarkable regenerative capacity in zebrafish through spontaneous reprogramming post-injury but remain limited in mammals. This review highlights the key mechanisms underlying Müller glia reprogramming, including gene regulatory networks, cytokine signaling, signal transduction pathways, epigenetic modifications, and transcriptional regulation. Cross-species analyses have uncovered conserved gene networks that suppress neurogenesis in mammals, while injury-induced transcriptional profiles reveal divergent regenerative strategies. Combinatorial approaches may enhance the reprogramming of mammalian Müller glia into functional neurons. Nevertheless, significant challenges remain, such as variability in the efficacy of direct reprogramming methods and the limited regeneration of cone photoreceptors, even in regenerative species. We conclude that targeting epigenetic barriers and species-specific regulatory pathways offers promising avenues for clinical translation in retinal disorders such as glaucoma and retinitis pigmentosa. Moving forward, research efforts should prioritize the functional integration of regenerated neurons and the development of standardized methodologies to accelerate therapeutic advancements.https://www.mdpi.com/2571-6980/6/2/20Müller gliareprogrammingdifferentiationretinal regenerationneuron
spellingShingle Yuyan Zhou
Song Qin
Haixiang Wu
Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron Regeneration
Neuroglia
Müller glia
reprogramming
differentiation
retinal regeneration
neuron
title Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron Regeneration
title_full Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron Regeneration
title_fullStr Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron Regeneration
title_full_unstemmed Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron Regeneration
title_short Advancements in Müller Glia Reprogramming: Pioneering Approaches for Retinal Neuron Regeneration
title_sort advancements in muller glia reprogramming pioneering approaches for retinal neuron regeneration
topic Müller glia
reprogramming
differentiation
retinal regeneration
neuron
url https://www.mdpi.com/2571-6980/6/2/20
work_keys_str_mv AT yuyanzhou advancementsinmullergliareprogrammingpioneeringapproachesforretinalneuronregeneration
AT songqin advancementsinmullergliareprogrammingpioneeringapproachesforretinalneuronregeneration
AT haixiangwu advancementsinmullergliareprogrammingpioneeringapproachesforretinalneuronregeneration