ArticleInvestigative ophthalmology & visual science2010
In glaucoma the upregulated truncated TrkC.T1 receptor isoform in glia causes increased TNF-alpha production, leading to retinal ganglion cell death.
Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions.Frontiers in neuroscience · 2022Pooled it
- Selective inhibitors of the TrkC.T1 receptor reduce retinal inflammation and delay neuronal death in a model of retinitis pigmentosa.PNAS nexus · 2025Article
- High Intraocular Concentration of Fibrinogen Regulates Retinal Function Via the ICAM-1 Pathway.Investigative ophthalmology & visual science · 2024Article
- Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review).Molecular medicine reports · 2024Review
- Smart Contact Lenses as Wearable Ophthalmic Devices for Disease Monitoring and Health Management.Chemical reviews · 2023Review
- Vision protection and robust axon regeneration in glaucoma models by membrane-associated Trk receptors.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Human-Induced Pluripotent Stem Cell-Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2022Review
- Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system.Frontiers in immunology · 2022Review
- Article
- The Neurotrophin Receptor TrkC as a Novel Molecular Target of the Antineuroblastoma Action of Valproic Acid.International journal of molecular sciences · 2021Article
- Neuroprotection: Pro-survival and Anti-neurotoxic Mechanisms as Therapeutic Strategies in Neurodegeneration.Frontiers in cellular neuroscience · 2019Review
- Article
- In retinitis pigmentosa TrkC.T1-dependent vectorial Erk activity upregulates glial TNF-α, causing selective neuronal death.Cell death & disease · 2017Article
- Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain.International journal of molecular sciences · 2017Review
- Interferon-β Inhibits Neurotrophin 3 Signalling and Pro-Survival Activity by Upregulating the Expression of Truncated TrkC-T1 Receptor.Molecular neurobiology · 2017Article
- Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis.Cell death & disease · 2016Article
- p75NTR and Its Ligand ProNGF Activate Paracrine Mechanisms Etiological to the Vascular, Inflammatory, and Neurodegenerative Pathologies of Diabetic Retinopathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- The Paradoxical Signals of Two TrkC Receptor Isoforms Supports a Rationale for Novel Therapeutic Strategies in ALS.PloS one · 2016Article
- Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina.Investigative ophthalmology & visual science · 2015Article
- Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
purposeGlaucoma is a distinct neuropathy characterized by the chronic and progressive death of retinal ganglion cells (RGCs). The etiology of RGC death remains unknown. Risk factors for glaucomatous RGC death are elevated intraocular pressure and glial production of tumor necrosis factor-alpha (TNF-α). Previously, the authors showed that glaucoma causes a rapid upregulation of a neurotrophin receptor truncated isoform lacking the kinase domain, TrkC.T1, in retina. Here they examined the biological role of TrkC.T1 during glaucoma progression.
methodsRat and mouse models of chronic ocular hypertension were used. Immunofluorescence Western blot analysis and in situ mRNA hybridization were used to identify cells upregulating TrkC.T1. A genetic model of engineered mice lacking TrkC.T1 (TrkC.T1(-/-)) was used to validate a role for this receptor in glaucoma. Pharmacologic studies were conducted to evaluate intravitreal delivery of agonists or antagonists of TrkC.T1, compared with controls, during glaucoma. Surviving RGCs were quantified by retrograde-labeling techniques. Production of neurotoxic TNF-α and α2 macroglobulin were quantified.
resultsTrkC.T1 was upregulated in retinal glia, with a pattern similar to that of TNF-α. TrkC.T1(-/-) mice had normal retinas. However, during experimental glaucoma, TrkC.T1(-/-) mice had lower rates of RGC death and produced less TNF-α than wild-type littermates. In rats with glaucoma, the pharmacologic use of TrkC antagonists delayed RGC death and reduced the production of retinal TNF-α.
conclusionsTrkC.T1 is implicated in glaucomatous RGC death through the control of glial TNF-α production. Overall, the data point to a paracrine mechanism whereby elevated intraocular pressure upregulated glial TrkC.T1 expression in glia; TrkC.T1 controlled glial TNF-α production, and TNF-α caused RGC death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.