ArticleThe American journal of pathology2009
Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 152 citations in OpenAlex.
- Wnt Pathway Agonism as a Therapeutic Strategy for Retinal Vascular Diseases: A Narrative Review of Evidence to Date.Ophthalmology and therapy · 2026Review
- Endothelial dysfunction in human diabetic vascular complications: translating single-cell transcriptomics into therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- The Wnt/StarD7 axis protects retinal ganglion cells from glutamate excitotoxicity by inhibiting ferroptosis.Biology direct · 2026Article
- Serial Aqueous Humor Proteomics in Diabetic Macular Edema: Correlation of Novel Targets with Retinal Fluid Volume.Ophthalmology science · 2026Article
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Wnt/β-Catenin Signaling in Diabetic Complications: Mechanisms and Therapeutic Potential.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- The Therapeutic Effect of a Biodegradable Long-Acting Intravitreal Implant Containing CGK012 on Neovascular Age-Related Macular Degeneration by Promoting β-Catenin Degradation.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Plasma multi-omics and machine learning reveal predictive biomarkers for type 2 diabetes and retinopathy in Qatar biobank cohort.Journal of translational medicine · 2025Article
- Ref-1 redox activity modulates canonical Wnt signaling in endothelial cells.Redox biology · 2025Article
- YBX1-driven TUBB6 upregulation facilitates ocular angiogenesis via WNT3A-FZD8 pathway.Theranostics · 2025Article
- The multifaceted role of kallistatin in human diseases: mechanistic insights and translational potential.Frontiers in cardiovascular medicine · 2025Review
- Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.Investigative ophthalmology & visual science · 2024Article
- Design principles and therapeutic applications of novel synthetic WNT signaling agonists.iScience · 2024Review
- The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.Genes & diseases · 2024Review
- Article
- Shared signaling pathways and comprehensive therapeutic approaches among diabetes complications.Frontiers in medicine · 2024Review
- Pharmacological Modulation of β-Catenin Preserves Endothelial Barrier Integrity and Mitigates Retinal Vascular Permeability and Inflammation.Journal of clinical medicine · 2023Article
- Wg/Wnt1 and Erasp link ER stress to proapoptotic signaling in an autosomal dominant retinitis pigmentosa model.Experimental & molecular medicine · 2023Article
- Potential disease biomarkers for diabetic retinopathy identified through Mendelian randomization analysis.Frontiers in endocrinology · 2023Article
- Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases.Pharmaceutics · 2022Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Although Wnt signaling is known to mediate multiple biological and pathological processes, its association with diabetic retinopathy (DR) has not been established. Here we show that retinal levels and nuclear translocation of beta-catenin, a key effector in the canonical Wnt pathway, were increased in humans with DR and in three DR models. Retinal levels of low-density lipoprotein receptor-related proteins 5 and 6, coreceptors of Wnts, were also elevated in the DR models. The high glucose-induced activation of beta-catenin was attenuated by aminoguanidine, suggesting that oxidative stress is a direct cause for the Wnt pathway activation in diabetes. Indeed, Dickkopf homolog 1, a specific inhibitor of the Wnt pathway, ameliorated retinal inflammation, vascular leakage, and retinal neovascularization in the DR models. Dickkopf homolog 1 also blocked the generation of reactive oxygen species induced by high glucose, suggesting that Wnt signaling contributes to the oxidative stress in diabetes. These observations indicate that the Wnt pathway plays a pathogenic role in DR and represents a novel therapeutic target.
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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.