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Updated: Sep 6, 2026
Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
Published on: October 27, 2017
Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer
Eun Jung Lee1,2,3, Museong Kim1,2, Sooyeon Park1,2,3
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
Abstract:
Individuals with retinal degenerative diseases struggle to restore vision due to the inability to regenerate retinal cells. Unlike cold-blooded vertebrates, mammals lack Müller glia (MG)-mediated retinal regeneration, indicating the limited regenerative capacity of mammalian MG. Here, we identify prospero-related homeobox 1 (Prox1) as a key factor restricting this process. Prox1 accumulates in MG of degenerating human and mouse retinas but not in regenerating zebrafish. In mice, Prox1 in MG originates from neighboring retinal neurons via intercellular transfer. Blocking this transfer enables MG reprogramming into retinal progenitor cells in injured mouse retinas. Moreover, adeno-associated viral delivery of an anti-Prox1 antibody, which sequesters extracellular Prox1, promotes retinal neuron regeneration and delays vision loss in a retinitis pigmentosa model. These findings establish Prox1 as a barrier to MG-mediated regeneration and highlight anti-Prox1 therapy as a promising strategy for restoring retinal regeneration in mammals.
Insights
Mammals cannot regenerate retinal cells like cold-blooded vertebrates because of the protein prospero-related homeobox 1 (Prox1). Blocking Prox1 in Müller glia (MG) promotes retinal regeneration, offering a potential therapy for vision loss.
Area of Science:
- Ophthalmology
- Developmental Biology
- Regenerative Medicine
Background:
- Retinal degenerative diseases cause irreversible vision loss due to limited regeneration of retinal cells in mammals.
- Mammalian Müller glia (MG) possess limited regenerative capacity compared to zebrafish, hindering vision restoration.
- The molecular mechanisms restricting mammalian MG regeneration remain largely unknown.
Purpose of the Study:
- To identify key factors inhibiting Müller glia (MG)-mediated retinal regeneration in mammals.
- To investigate the role of prospero-related homeobox 1 (Prox1) in restricting mammalian retinal regeneration.
- To explore therapeutic strategies targeting Prox1 for vision restoration in retinal degenerative diseases.
Main Methods:
- Comparative analysis of Prox1 expression in degenerating human/mouse retinas versus regenerating zebrafish retinas.
- Investigation of intercellular transfer of Prox1 from retinal neurons to MG in mice.
- Experimental blocking of Prox1 transfer and administration of anti-Prox1 antibodies via adeno-associated virus (AAV) vectors.
- Assessment of MG reprogramming into retinal progenitor cells and retinal neuron regeneration in mouse models of retinal injury and retinitis pigmentosa.
Main Results:
- Prox1 accumulates in MG of degenerating mammalian retinas but is absent in regenerating zebrafish retinas.
- Prox1 is transferred intercellularly to MG from neighboring retinal neurons in mice.
- Inhibiting Prox1 transfer or sequestering extracellular Prox1 with an antibody promotes MG reprogramming and retinal neuron regeneration in injured mouse retinas.
- Anti-Prox1 therapy delayed vision loss in a mouse model of retinitis pigmentosa.
Conclusions:
- Prospero-related homeobox 1 (Prox1) acts as a critical barrier to Müller glia (MG)-mediated retinal regeneration in mammals.
- Intercellular transfer of Prox1 from neurons to MG is a key mechanism restricting regeneration.
- Targeting Prox1 with therapies like anti-Prox1 antibodies shows promise for restoring retinal regeneration and treating vision loss in degenerative diseases.
