ArticleMolecular neurodegeneration2021
The TGFβ/Notch axis facilitates Müller cell-to-epithelial transition to ultimately form a chronic glial scar.
Article in Molecular neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Distinct mechanisms of electroacupuncture and manual acupuncture in modulating hypothalamic GnRH-tanycyte unit function of polycystic ovary syndrome.Chinese medicine · 2025Article
- Targeting tRNA-Derived Non-Coding RNA Alleviates Diabetes-Induced Visual Impairment through Protecting Retinal Neurovascular Unit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulating Integrin β1 to Restore Gonadotropin-Releasing Hormone-Tanycyte Unit Function in Polycystic Ovary Syndrome-Related Hypothalamic Dysregulation.Research (Washington, D.C.) · 2025Article
- Drugs targeting TGF-β/Notch interaction attenuate hypertrophic scar formation by optic atrophy 1-mediated mitochondrial fusion.Molecular and cellular biochemistry · 2024Article
- Macrophages coordinate immune response to laser-induced injury via extracellular traps.Journal of neuroinflammation · 2024Article
- Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy.International journal of biological sciences · 2024Article
- The mechanics of the retina: Müller glia role on retinal extracellular matrix and modelling.Frontiers in medicine · 2024Review
- Assessing the role of T cells in response to retinal injury to uncover new therapeutic targets for the treatment of retinal degeneration.Journal of neuroinflammation · 2023Article
- γ-Secretase fanning the fire of innate immunity.Biochemical Society transactions · 2023Review
- Characterization of Macroglia Response during Tissue Repair in a Laser-Induced Model of Retinal Degeneration.International journal of molecular sciences · 2023Article
- Regenerative capacity of Müller cells and their modulation as a tool to treat retinal degenerations.Neural regeneration research · 2023Article
- Heterogeneity in quiescent Müller glia in the uninjured zebrafish retina drive differential responses following photoreceptor ablation.Frontiers in molecular neuroscience · 2023Article
- Article
- Harnessing the Neuroprotective Behaviors of Müller Glia for Retinal Repair.Frontiers in bioscience (Landmark edition) · 2022Review
- IFN-γ promotes the development of systemic lupus erythematosus through the IFNGR1/2-PSTAT1-TBX21 signaling axis.American journal of translational research · 2022Article
- Retina regeneration: lessons from vertebrates.Oxford open neuroscience · 2022Review
- Cellular and molecular alterations in neurons and glial cells in inherited retinal degeneration.Frontiers in neuroanatomy · 2022Review
- Genetic and epigenetic regulators of retinal Müller glial cell reprogramming.Advances in ophthalmology practice and researchReview
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundContrasting with zebrafish, retinal regeneration from Müller cells (MCs) is largely limited in mammals, where they undergo reactive gliosis that consist of a hypertrophic response and ultimately results in vision loss. Transforming growth factor β (TGFβ) is essential for wound healing, including both scar formation and regeneration. However, targeting TGFβ may affect other physiological mechanisms, owing its pleiotropic nature. The regulation of various cellular activities by TGFβ relies on its interaction with other pathways including Notch. Here, we explore the interplay of TGFβ with Notch and how this regulates MC response to injury in zebrafish and mice. Furthermore, we aimed to characterize potential similarities between murine and human MCs during chronic reactive gliosis.
methodsFocal damage to photoreceptors was induced with a 532 nm diode laser in TgBAC (gfap:gfap-GFP) zebrafish (ZF) and B6-Tg (Rlbp1-GFP) mice. Transcriptomics, immunofluorescence, and flow cytometry were employed for a comparative analysis of MC response to laser-induced injury between ZF and mouse. The laser-induced injury was paired with pharmacological treatments to inhibit either Notch (DAPT) or TGFβ (Pirfenidone) or TGFβ/Notch interplay (SIS3). To determine if the murine laser-induced injury model translates to the human system, we compared the ensuing MC response to human donors with early retinal degeneration.
resultsInvestigations into injury-induced changes in murine MCs revealed TGFβ/Notch interplay during reactive gliosis. We found that TGFβ1/2 and Notch1/2 interact via Smad3 to reprogram murine MCs towards an epithelial lineage and ultimately to form a glial scar. Similar to what we observed in mice, we confirmed the epithelial phenotype of human Müller cells during gliotic response.
conclusionThe study indicates a pivotal role for TGFβ/Notch interplay in tuning MC stemness during injury response and provides novel insights into the remodeling mechanism during retinal degenerative diseases.
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