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Updated: Sep 29, 2025
Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
Published on: October 27, 2017
Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina
Raquel R Martins1, Mazen Zamzam2, Dhani Tracey-White3
1The Bateson Centre, Healthy Lifespan Institute, MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing and Department of Oncology and Metabolism, University of Sheffield Medical School, Sheffield, UK.
Abstract:
Ageing is a significant risk factor for degeneration of the retina. Müller glia cells (MG) are key for neuronal regeneration, so harnessing the regenerative capacity of MG in the retina offers great promise for the treatment of age-associated blinding conditions. Yet, the impact of ageing on MG regenerative capacity is unclear. Here, we show that the zebrafish retina undergoes telomerase-independent, age-related neurodegeneration but that this is insufficient to stimulate MG proliferation and regeneration. Instead, age-related neurodegeneration is accompanied by MG morphological aberrations and loss of vision. Mechanistically, yes-associated protein (Yap), part of the Hippo signalling, has been shown to be critical for the regenerative response in the damaged retina, and we show that Yap expression levels decline with ageing. Despite this, morphologically and molecularly altered aged MG retain the capacity to regenerate neurons after acute light damage, therefore, highlighting key differences in the MG response to high-intensity acute damage versus chronic neuronal loss in the zebrafish retina.
Insights
Ageing impairs retinal Müller glia (MG) regenerative potential, leading to vision loss. However, aged MG can still regenerate neurons after acute damage, revealing distinct responses to chronic versus acute retinal injury.
Area of Science:
- Ophthalmology and Vision Science
- Neuroscience
- Cell Biology
Background:
- Ageing is a primary risk factor for retinal degeneration and vision loss.
- Müller glia (MG) are crucial for retinal regeneration, offering therapeutic potential for age-associated blinding conditions.
- The effect of ageing on MG regenerative capacity remains largely unknown.
Purpose of the Study:
- To investigate the impact of ageing on Müller glia regenerative capacity in the zebrafish retina.
- To elucidate the mechanisms underlying age-related retinal degeneration and Müller glia dysfunction.
- To compare Müller glia responses to chronic age-related neurodegeneration versus acute light-induced damage.
Main Methods:
- Analysis of age-related neurodegeneration in zebrafish retinas.
- Assessment of Müller glia proliferation and morphological changes with ageing.
- Investigation of the role of Yes-associated protein (Yap) and Hippo signaling in aged Müller glia.
- Evaluation of Müller glia regenerative potential following acute light damage in aged zebrafish.
Main Results:
- Zebrafish retinas exhibit telomerase-independent, age-related neurodegeneration insufficient to trigger Müller glia proliferation.
- Age-related neurodegeneration is associated with Müller glia morphological abnormalities and vision impairment.
- Yes-associated protein (Yap) expression, critical for retinal regeneration, declines with ageing.
- Despite age-related alterations, Müller glia retain the ability to regenerate neurons after acute light damage.
Conclusions:
- Ageing compromises Müller glia's intrinsic regenerative capacity in response to chronic neurodegeneration.
- Age-related Müller glia dysfunction involves morphological changes and reduced Yap expression.
- Aged Müller glia exhibit differential regenerative responses to acute injury compared to chronic degeneration, highlighting distinct cellular mechanisms.
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