ArticleInternational journal of molecular sciences2014
Intravitreal injection of ranibizumab and CTGF shRNA improves retinal gene expression and microvessel ultrastructure in a rodent model of diabetes.
Article in International journal of molecular sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Targeting the Eye: RNA-Based Therapies, Interferences, and Delivery Strategies.Pharmaceutics · 2025Review
- The Long-Standing Problem of Proliferative Retinopathies: Current Understanding and Critical Cues.Cells · 2025Review
- Nanomaterial-Based Anti-Angiogenic Gene Therapy for Retinal Neovascular Diseases: Mechanistic Insights and Preclinical Advances.International journal of nanomedicine · 2025Review
- A Nucleic Acid-Based LYTAC Plus Platform to Simultaneously Mediate Disease-Driven Protein Downregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy.International journal of ophthalmology · 2024Article
- Blue light exposure collapses the inner blood-retinal barrier by accelerating endothelial CLDN5 degradation through the disturbance of GNAZ and the activation of ADAM17.Fluids and barriers of the CNS · 2023Article
- Dynamin-like Protein 1 (DNML1) as a Molecular Target for Antibody-Based Immunotherapy to Treat Glaucoma.International journal of molecular sciences · 2022Article
- Experiment-Based Interventions to Diabetic Retinopathy: Present and Advances.International journal of molecular sciences · 2022Review
- A Monoclonal Anti-HMGB1 Antibody Attenuates Neurodegeneration in an Experimental Animal Model of Glaucoma.International journal of molecular sciences · 2022Article
- Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.Acta pharmaceutica Sinica. B · 2022Review
- Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications.International journal of nanomedicine · 2022Review
- Article
- RNA sequencing reveals BMP4 as a basis for the dual-target treatment of diabetic retinopathy.Journal of molecular medicine (Berlin, Germany) · 2021Article
- The Aflibercept-Induced MicroRNA Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients Detected by Next-Generation Sequencing.Frontiers in pharmacology · 2021Article
- Isoliquiritigenin downregulates miR-195 and attenuates oxidative stress and inflammation in STZ-induced retinal injury.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration.International journal of molecular sciences · 2020Review
- Proteomic Biomarkers of Retinal Inflammation in Diabetic Retinopathy.International journal of molecular sciences · 2019Review
- Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies.Expert opinion on biological therapy · 2018Review
- Regulation and bioactivity of the CCN family of genes and proteins in obesity and diabetes.Journal of cell communication and signaling · 2018Review
- Research progress on the role of connective tissue growth factor in fibrosis of diabetic retinopathy.International journal of ophthalmology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF) in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore, in this study, we employ a novel dual-target intervention that involves intravitreal injection of the VEGF inhibitor ranibizumab and a transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin RNA (shRNA) driven by human RNA polymerase III promoter U6. The effects of the dual-target intervention on the expression of VEGF and CTGF and on microvessel ultrastructure were examined in retina of streptozocin-induced diabetic rats. CTGF was significantly up-regulated at week 8 after diabetic induction, whereas VEGF was not up-regulated until week 10. The high expression of both genes was maintained at week 12. Transmission electron microscopy also revealed progressive exacerbation of microvessel ultrastructure during the same period. In addition, ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas. Importantly, dual-target intervention normalized the transcript levels of both target genes and ameliorated retinal microvessel ultrastructural damage better than either single-target intervention. These results suggest the advantages of dual-target over single-target interventions in diabetic retina and reveal a novel therapeutic modality for diabetic retinopathy.
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