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Updated: May 1, 2026
Isolation of Primary Mouse Retinal Glial Müller Cells
Published on: August 30, 2024
Proliferation potential of Müller glia after retinal damage varies between mouse strains
Akiko Suga1, Kazuyo Sadamoto1, Momo Fujii1
1Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Minatojima, Chu-O-ku, Kobe, Japan.
Abstract:
Retinal Müller glia can serve as a source for regeneration of damaged retinal neurons in fish, birds and mammals. However, the proliferation rate of Müller glia has been reported to be low in the mammalian retina. To overcome this problem, growth factors and morphogens have been studied as potent promoters of Müller glial proliferation, but the molecular mechanisms that limit the proliferation of Müller glia in the mammalian retina remain unknown. In the present study, we found that the degree of damage-induced Müller glia proliferation varies across mouse strains. In mouse line 129×1/SvJ (129), there was a significantly larger proliferative response compared with that observed in C57BL/6 (B6) after photoreceptor cell death. Treatment with a Glycogen synthase kinase 3 (GSK3) inhibitor enhanced the proliferation of Müller glia in 129 but not in B6 mouse retinas. We therefore focused on the different gene expression patterns during retinal degeneration between B6 and 129. Expression levels of Cyclin D1 and Nestin correlated with the degree of Müller glial proliferation. A comparison of genome-wide gene expression between B6 and 129 showed that distinct sets of genes were upregulated in the retinas after damage, including immune response genes and chromatin remodeling factors.
Insights
Mammalian retinal Müller glia have limited proliferation for neuron regeneration. This study reveals strain-specific differences in Müller glial proliferation and identifies gene expression patterns, including immune response and chromatin remodeling factors, that influence this regenerative capacity.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Ophthalmology
Background:
- Retinal Müller glia are crucial for retinal neuron regeneration in various species.
- Mammalian Müller glial proliferation is typically limited, hindering regenerative potential.
- Molecular mechanisms controlling mammalian Müller glial proliferation remain largely unknown.
Purpose of the Study:
- To investigate the molecular mechanisms underlying limited Müller glial proliferation in the mammalian retina.
- To identify factors influencing strain-specific differences in Müller glial proliferative responses to retinal damage.
- To explore potential therapeutic targets for enhancing retinal regeneration.
Main Methods:
- Comparative analysis of Müller glial proliferation in different mouse strains (129×1/SvJ and C57BL/6) following photoreceptor cell death.
- Pharmacological intervention using a Glycogen synthase kinase 3 (GSK3) inhibitor.
- Genome-wide gene expression profiling to identify differentially expressed genes.
- Correlation analysis of gene expression (Cyclin D1, Nestin) with Müller glial proliferation.
Main Results:
- Significant variation in damage-induced Müller glial proliferation was observed between mouse strains.
- Mouse line 129×1/SvJ exhibited a greater proliferative response than C57BL/6.
- GSK3 inhibition enhanced Müller glial proliferation in 129×1/SvJ but not in C57BL/6 retinas.
- Expression of Cyclin D1 and Nestin correlated with the extent of Müller glial proliferation.
- Distinct sets of immune response and chromatin remodeling genes were upregulated in damaged retinas, varying by mouse strain.
Conclusions:
- Strain-specific genetic factors significantly influence Müller glial proliferative capacity in response to retinal injury.
- GSK3 signaling plays a role in regulating Müller glial proliferation, with differential effects across mouse strains.
- Understanding these molecular differences is key to developing strategies for enhancing retinal regeneration in mammals.
