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Learning from regenerators · Müller glia

The eye's built-in repair cells.

Müller glia are specialised support cells in the retina. In zebrafish they can switch from supporting neurons to producing new ones, helping to rebuild damaged retinal tissue. In mammals, that switch is largely missing.

Established: supported by the published scientific literature
Illustration of a zebrafish eye with a magnified cross-section of the retina showing ganglion cells, bipolar cells, Müller glia and photoreceptors, and a single Müller glia cell spanning the retina.
Cross-section of the zebrafish retina and a single Müller glia cell. Illustration, not to scale.

At a glance

Cell type
Retinal glia (support cells)
Found in
The retina of all vertebrates
In zebrafish
Can regenerate all major retinal neurons
In mammals
Limited neurogenic response

Up close

Region by region, magnified.

What each highlighted part of the retina can do, how it does it and what the research shows.

Illustration of a single Müller glia cell stretching from the inner to the outer retina

01 The cell

A cell that spans the whole retina.

Each Müller glia cell stretches across the full depth of the retina, from its inner to its outer surface, in contact with the neurons around it.

Normal role
Maintaining the retina's stability and integrity, acting as a scaffold and support for neurons.
Development
One of the last retinal cell types to be born during development.
After injury
In mammals, the response can be protective or harmful to retinal function. In zebrafish, the cell is reprogrammed into a regenerative state.

Source: Goldman, 2014

Magnified illustration of a cross-section of the zebrafish retina with its layers of neurons

02 Retinal layers

The layers it supports.

The retina is organised in layers, each with a different job in turning light into a signal the brain can use.

  • Photoreceptors detect light.
  • Bipolar cells process and relay visual information.
  • Ganglion cells send nerve signals to the brain through the optic nerve.
  • Müller glia run through all of these layers as the central support cell.
Magnified illustration of a zebrafish eye

03 Regeneration

From support to stem cell.

In zebrafish, Müller glia behave as retinal stem cells. After injury they are reprogrammed and generate progenitors that replace lost neurons.

Everyday renewal
Even in the uninjured zebrafish retina, Müller glia divide occasionally and produce progenitors that make new rod photoreceptors.
After injury
Reprogrammed Müller glia produce a proliferating population of progenitors that can regenerate all major retinal cell types and restore vision.
Targeted repair
When cone photoreceptors are lost, Müller glia-derived progenitors specifically regenerate the missing cones.

Source: Bernardos et al., 2007; Goldman, 2014

04 In mammals

The mammalian gap.

Mammalian Müller glia can be coaxed to divide and make neurons under special circumstances, but the natural response is too weak to repair a damaged retina.

What limits them
In mice, Müller glia lose their capacity to make neurons as they mature. This loss is accompanied by reduced chromatin accessibility, suggesting epigenetic factors limit regeneration.
What has been shown
In adult mice, forcing Müller glia to express the gene Ascl1, together with a histone deacetylase inhibitor, produced new neurons after retinal injury. The new neurons connected to existing ones and responded to light.
What it suggests
The capacity may be held back rather than absent, a question that is still under investigation.

Source: Goldman, 2014; Jorstad et al., 2017

Proposed: a framework or hypothesis Dimzang is proposing and investigating

Why it matters to us.

Mammals keep the same cell type that rebuilds the zebrafish retina. Our first research output is a framework on why the Müller glia response differs between strong regenerators and adult mammals. It will be posted as a preprint, not a peer-reviewed publication.

Our regeneration research Collaborate with us

Sources

Where this comes from.

  1. Goldman D. Müller glial cell reprogramming and retina regeneration. Nature Reviews Neuroscience. 2014;15(7):431–442. doi.org/10.1038/nrn3723
  2. Bernardos RL, Barthel LK, Meyers JR, Raymond PA. Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. Journal of Neuroscience. 2007;27(26):7028–7040. doi.org/10.1523/JNEUROSCI.1624-07.2007
  3. Jorstad NL, Wilken MS, Grimes WN, et al. Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature. 2017;548(7665):103–107. doi.org/10.1038/nature23283

Summaries are simplified for a general audience. Illustrations are artistic, not anatomical drawings.

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