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Updated: Mar 24, 2026
Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
Published on: October 27, 2017
DNA Damage Response in Proliferating Müller Glia in the Mammalian Retina
Kaori Nomura-Komoike1, Fuminori Saitoh1, Yuta Komoike2
1Department of Anatomy School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Purpose:
Müller glia, the principal glial cell type in the retina, have the potential to proliferate and regenerate neurons after retinal damage. However, unlike the situation in fish and birds, this capacity of Müller glia is extremely limited in mammals. To gain new insights into the mechanisms that hamper retinal regeneration in mammals, we examined the cell cycle progression and DNA damage response in Müller glia after retinal damage.
Methods:
Expression of cell cycle-related proteins and DNA damage response were analyzed in adult rat and mouse retinas after N-methyl-N-nitrosourea (MNU)- or N-methyl-D-aspartate (NMDA)-induced retinal damage. Zebrafish and postnatal rat retinas were also investigated for comparison. Analysis was conducted by using immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction.
Results:
In the rat retina, most Müller glia reentered the cell cycle after MNU-induced photoreceptor damage while no proliferative response was observed in the mouse model. Cell cycle reentry of rat Müller glia was accompanied by DNA damage response including the phosphorylation of the histone variant H2AX and upregulation of p53 and p21. The DNA damage response was also observed in rat Müller glia after NMDA-induced loss of inner retinal neurons, but not in zebrafish Müller glia or rat retinal progenitor cells.
Conclusions:
Our findings suggest that the DNA damage response induced by unscheduled cell cycle reentry may be one of the mechanisms that limit the proliferative and regenerative capacity of Müller glia in the mammalian retina.
Insights
Mammalian Müller glia (retinal support cells) show limited regeneration potential. A DNA damage response upon cell cycle reentry appears to restrict their ability to proliferate and repair retinal damage.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Müller glia are the primary glial cells in the retina.
- They possess regenerative potential in non-mammalian vertebrates but limited capacity in mammals.
- Understanding these limitations is key to enhancing retinal repair in mammals.
Purpose of the Study:
- To investigate the cell cycle progression of Müller glia post-retinal damage.
- To analyze the DNA damage response in Müller glia in mammalian retinas.
- To identify mechanisms hindering mammalian retinal regeneration.
Main Methods:
- Adult rat and mouse retinas subjected to chemical-induced retinal damage (MNU or NMDA).
- Analysis of cell cycle proteins and DNA damage markers using immunofluorescence, Western blotting, and qRT-PCR.
- Comparative analysis with zebrafish and postnatal rat retinas.
Main Results:
- Rat Müller glia reentered the cell cycle after photoreceptor damage (MNU), unlike in mice.
- Cell cycle reentry in rat Müller glia triggered DNA damage responses (H2AX phosphorylation, p53/p21 upregulation).
- Similar DNA damage response observed after inner retinal neuron loss (NMDA) in rats, but not in zebrafish or rat progenitor cells.
Conclusions:
- The DNA damage response in Müller glia may limit their proliferative capacity in mammals.
- This response is linked to unscheduled cell cycle reentry after retinal injury.
- Findings highlight a critical barrier to Müller glia-mediated retinal regeneration in mammals.
