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Updated: Jan 28, 2026

Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
Published on: October 27, 2017
Retinal microglia signaling affects Müller cell behavior in the zebrafish following laser injury induction
Federica Maria Conedera1,2,3, Ana Maria Quintela Pousa1,2, Nadia Mercader4
1Department of Ophthalmology, University Hospital of Bern, University of Bern, Bern, Switzerland.
Abstract:
Microglia are the resident tissue macrophages of the central nervous system including the retina. Under pathophysiological conditions, microglia can signal to Müller cells, the major glial component of the retina, affecting their morphological, molecular, and functional responses. Microglia-Müller cell interactions appear to be bidirectional shaping the overall injury response in the retina. Hence, microglia and Müller cell responses to disease and injury have been ascribed both positive and negative outcomes. However, Müller cell reactivity and survival in the absence of immune cells after injury have not been investigated in detail in adult zebrafish. Here, we develop a model of focal retinal injury combined with pharmacological treatments for immune cell depletion in zebrafish. The retinal injury was induced by a diode laser to damage photoreceptors. Two pharmacological treatments were used to deplete either macrophage-microglia (PLX3397) or selectively eliminate peripheral macrophages (clodronate liposomes). We show that PLX3397 treatment hinders retinal regeneration in zebrafish, which is reversed by microglial repopulation. On the other hand, selective macrophage elimination did not affect the kinetics of retinal regeneration. The absence of retinal microglia and macrophages leads to dysregulated Müller cell behavior. In the untreated fish, Müller cells react after injury induction showing glial fibrillary acidic protein (GFAP), Phospho-p44/42 MAPK (Erk1/2), and PCNA upregulation. However, in the immunosuppressed animals, GFAP and phospho-p44/42 MAPK (Erk1/2) expression was not upregulated overtime and the reentry in the cell cycle was not affected. Thus, microglia and Müller cell signaling is pivotal to unlock the regenerative potential of Müller cells in order to repair the damaged retina.
Insights
Microglia and Müller cells are crucial for retinal repair in zebrafish. Depleting microglia impairs regeneration, highlighting their vital role in Müller cell responses and unlocking retinal regenerative potential.
Area of Science:
- Neuroscience
- Ophthalmology
- Immunology
Background:
- Microglia, the central nervous system's resident macrophages, interact with Müller cells, the primary glial cells in the retina.
- These bidirectional microglia-Müller cell interactions influence retinal injury responses, with both beneficial and detrimental outcomes reported.
- The specific role of Müller cell reactivity and survival in the absence of immune cells post-injury in adult zebrafish remains underexplored.
Purpose of the Study:
- To investigate Müller cell behavior and retinal regeneration in adult zebrafish following focal injury and immune cell depletion.
- To elucidate the necessity of microglia and macrophages for Müller cell reactivity and regenerative processes in the injured retina.
Main Methods:
- Developed a focal retinal injury model in adult zebrafish using diode laser to damage photoreceptors.
- Employed pharmacological agents: PLX3397 for macrophage-microglia depletion and clodronate liposomes for selective peripheral macrophage elimination.
- Assessed Müller cell responses by analyzing glial fibrillary acidic protein (GFAP), Phospho-p44/42 MAPK (Erk1/2), and PCNA expression, alongside cell cycle reentry.
Main Results:
- PLX3397-induced depletion of microglia and macrophages significantly hindered retinal regeneration, an effect reversed upon microglial repopulation.
- Selective elimination of peripheral macrophages did not alter the kinetics of retinal regeneration.
- Absence of retinal microglia and macrophages led to dysregulated Müller cell behavior, characterized by suppressed GFAP and Erk1/2 upregulation and unaffected cell cycle reentry post-injury.
Conclusions:
- Microglia-Müller cell signaling is essential for activating Müller cell regenerative potential in the damaged retina.
- Microglia play a pivotal role in orchestrating Müller cell responses necessary for effective retinal repair in zebrafish.
- Targeting microglia-Müller cell interactions could be a key strategy for enhancing retinal regeneration.
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