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Endothelin2 Induces Expression of Genes Associated with Reactive Gliosis in Retinal Müller Cells
Vijay P Sarthy1, Hari Sawkar1, V Joseph Dudley1
1a Department of Ophthalmology , Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
Purpose/Aim Of The Study:
Photoreceptor degeneration is normally accompanied by reactive gliosis and gene expression changes in Müller (glial) cells. The signaling pathway involved inducing these changes in Müller cells is not known. It has been proposed that endothelin2 (EDN2) released by degenerating photoreceptors might induce gliotic changes in Müller cells. In the present study, we directly tested the hypothesis by determining whether treatment of Müller cell cultures with EDN2 results in upregulation of genes known to be expressed in activated Müller cells in vivo.
Materials And Methods:
Experiments were carried using an established rat Müller cell line (rMC-1), and gene expression was assessed by qRT-PCR.
Results:
We observed that EDN2 treatment upregulated transcripts for glial fibrillary acidic protein (Gfap), Serpina3n and endothelin receptor B (EdnrB), three genes associated with reactive gliosis in Müller cells. Ciliary neurotrophic factor (CNTF) treatment similarly led to induction of Gfap, Serpina3n and EdnrB transcripts, whereas glutamate treatment had no significant effect.
Conclusions:
The finding supports a role for EDN2 as a signaling agent between photoreceptors and Müller cells.
Insights
Endothelin2 (EDN2) signaling activates Müller cells, inducing genes linked to reactive gliosis. This suggests EDN2 acts as a crucial signal between photoreceptors and Müller cells during degeneration.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Photoreceptor degeneration typically involves reactive gliosis and altered gene expression in Müller cells.
- The specific signaling pathways responsible for Müller cell gliosis remain largely unknown.
- Endothelin2 (EDN2) released by dying photoreceptors is a proposed mediator of Müller cell gliosis.
Purpose of the Study:
- To investigate the role of endothelin2 (EDN2) in inducing Müller cell activation.
- To determine if EDN2 treatment upregulates genes associated with reactive gliosis in Müller cells.
Main Methods:
- Utilized a rat Müller cell line (rMC-1) for experimental studies.
- Assessed gene expression changes using quantitative real-time PCR (qRT-PCR).
Main Results:
- EDN2 treatment significantly upregulated transcripts for glial fibrillary acidic protein (Gfap), Serpina3n, and endothelin receptor B (EdnrB).
- These three genes are known markers of reactive gliosis in Müller cells.
- Ciliary neurotrophic factor (CNTF) also induced these genes, while glutamate had no significant effect.
Conclusions:
- The results support a role for EDN2 as a signaling molecule.
- EDN2 mediates communication between photoreceptors and Müller cells, particularly during retinal degeneration.
