ArticleDrug design, development and therapy2015
Effects of intravitreal injection of netrin-1 in retinal neovascularization of streptozotocin-induced diabetic rats.
Article in Drug design, development and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Endothelial UNC5B regulates blood‑retinal barrier homeostasis.International journal of molecular medicine · 2026Article
- Restoring compromised blood-retina-barrier integrity with Netrin-1 overexpression.Cellular and molecular life sciences : CMLS · 2025Article
- Optic Nerve Regeneration in Diabetic Retinopathy: Potentials and Challenges Ahead.International journal of molecular sciences · 2023Review
- Gαi1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.Theranostics · 2023Article
- Increased serum concentration of netrin-1 after intravitreal bevacizumab injection: is it a compensatory mechanism to counteract drug side effects?BMC ophthalmology · 2021Article
- Targeting Netrin-1 and -4 as a Novel Diagnostic Parameter and Treatment Option for Diabetic Retinopathy.Clinical ophthalmology (Auckland, N.Z.) · 2020Review
- Netrin-1 promotes epithelium repair in corneal injury.International journal of ophthalmology · 2020Article
- Pax 6 Controls Neural Crest Potential of Limbal Niche Cells to Support Self-Renewal of Limbal Epithelial Stem Cells.Scientific reports · 2019Article
- Air pollutant particulate matter 2.5 induces dry eye syndrome in mice.Scientific reports · 2018Article
- Rhamnazin attenuates inflammation and inhibits alkali burn-induced corneal neovascularization in rats.RSC advances · 2018Article
- Egr-1 increases angiogenesis in cartilage via binding Netrin-1 receptor DCC promoter.Journal of orthopaedic surgery and research · 2018Article
- Antiangiogenic effects of catalpol on rat corneal neovascularization.Molecular medicine reports · 2018Article
- Netrin as a Novel Biomarker and Its Therapeutic Implications in Diabetes Mellitus and Diabetes-Associated Complications.Journal of diabetes research · 2018Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn a previous study, we confirmed that netrin-1 acts as an antiangiogenic factor by inhibiting alkali burn-induced corneal neovascularization in rats. Here, we continue working on the role of netrin-1 in retinal neovascularization.
methodsUsing an in vitro angiogenesis assay, we detected the effects of netrin-1 on human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion at concentrations of 0.1 μg/mL or 5 μg/mL. We intravitreally injected 0.1 μg/mL or 5 μg/mL netrin-1 into streptozotocin-induced rats to assess retinal neovascularization using retinal electrophysiology and electroretinography, enzyme-linked immunosorbent assay, fundus fluoresce in angiography, measurement of inner blood retinal barrier, retinal hematoxylin-eosin staining, and retinal flat-mount fluorescence assays.
resultsHuman umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion were upregulated by netrin-1 at a concentration of 0.1 μg/mL (P<0.05), while 5 μg/mL netrin-1 had an opposite effect (P<0.05) in our in vitro angiogenesis assay. Retinal electrophysiology testing revealed that intravitreal injection of netrin-1 affected the amplitude of a- and b-waves (a-wave: 0.1 μg/mL netrin-1 =17.67±3.39 μm, 5 μg/mL netrin-1 =28.50±1.31 μm, phosphate-buffered saline [PBS]-treated =17.67±3.39 μm; b-wave: 0.1 μg/mL netrin-1 =44.67±4.80 μm, 5 μg/mL netrin-1 =97.17±9.63 μm, PBS-treated =44.67±4.80 μm) and the expression of VEGF-A (no-treatment rats, 9.29±0.80 pg/mL; PBS-treated rats, 19.64±3.77 pg/mL; 0.1 μg/mL netrin-1 treated rats, 21.37±3.64 pg/mL; 5 μg/mL netrin-1 treated rats, 9.85±0.54 pg/mL, at 6 weeks after induction). By comparing fluoresce in angiography, level of inner blood retinal barrier breakdown (% of control), retinal hematoxylin-eosin staining, and collagen-IV fluorescence assays in the retinas of PBS-treated rats, netrin-1 was found to suppress and reverse retinal neovascularization at a concentration of 5 μg/mL (P<0.05), while 0.1 μg/mL netrin-1 (P<0.05) led to an increase in the number of new retinal blood vessels, after 6 weeks' injection.
conclusionNetrin-1 could play a significant role in retinal neovascularization by dual-direction regulating angiogenesis dependent on dosage.
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