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Updated: Sep 21, 2026
Methylnitrosourea (MNU)-induced Retinal Degeneration and Regeneration in the Zebrafish: Histological and Functional Characteristics
Published on: October 20, 2014
Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells
Annaïg Hamon1, Christel Masson1, Juliette Bitard1
1Paris-Saclay Institute of Neuroscience, CNRS, Univ Paris-Sud, Université Paris-Saclay, Orsay, France 2Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France.
Purpose:
During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death.
Methods:
Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several differentially expressed genes were assessed by quantitative RT-PCR (RT-qPCR). Protein expression level and retinal cellular localization were determined by western blot and immunohistochemistry, respectively.
Results:
Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss.
Conclusions:
This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathologic conditions.
Insights
Researchers identified the Hippo/YAP pathway, including YAP and TEAD1, as key players in Müller glia response to photoreceptor degeneration. This finding offers new therapeutic targets for retinal diseases.
Area of Science:
- Retinal biology
- Cellular signaling pathways
- Neuroscience
Background:
- Müller glia cells are crucial for retinal health and respond to photoreceptor damage through reactive gliosis.
- Understanding Müller cell molecular responses is vital for developing therapies for retinal degeneration.
- The Hippo/YAP pathway's role in this process remains largely unexplored.
Purpose of the Study:
- To identify novel molecular factors involved in Müller cell reactions to photoreceptor death.
- To investigate the involvement of the Hippo/YAP signaling pathway in retinal degeneration.
Main Methods:
- Whole transcriptome sequencing of wild-type and rd10 mouse retinas.
- Quantitative RT-PCR (RT-qPCR) to validate mRNA expression changes.
- Western blot and immunohistochemistry to assess protein expression and localization.
Main Results:
- The Hippo/YAP pathway was significantly altered in degenerating rd10 retinas.
- YAP and TEAD1, downstream effectors of Hippo/YAP, are specifically expressed in Müller cells.
- Expression of YAP, TEAD1, Ctgf, and Cyr61 increased in reactive Müller glia during photoreceptor degeneration.
Conclusions:
- YAP and TEAD1 are specifically expressed in Müller cells and their expression is upregulated during retinal degeneration.
- The Hippo/YAP pathway is deregulated in reactive Müller cells under pathological conditions.
- This study reveals a novel role for the Hippo/YAP pathway in Müller cell response to photoreceptor loss.
