ArticleJournal of diabetes research2017
Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System.
Article in Journal of diabetes research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Inhibiting the uPAR/FPR1 interactions reduces blood-retinal barrier breakdown and improves retinal function in a rat model of diabetes.Frontiers in neuroscience · 2026Article
- Review
- Inhibiting The uPA/uPAR Pathway Affords Photoreceptor Resilience and Preserves Retinal Function in a Mouse Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- The Long-Standing Problem of Proliferative Retinopathies: Current Understanding and Critical Cues.Cells · 2025Review
- A Personal Scientific Journey in Ophthalmology: Twenty-Five Years of Translating Research into Novel Therapies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Turn-Adopting Peptidomimetic as a Formyl Peptide Receptor-1 Antagonist.ACS pharmacology & translational science · 2024Article
- Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator.Biomedicines · 2024Review
- Cell and molecular targeted therapies for diabetic retinopathy.Frontiers in endocrinology · 2024Review
- Identifying the stability of housekeeping genes to be used for the quantitative real-time PCR normalization in retinal tissue of streptozotocin-induced diabetic rats.International journal of ophthalmology · 2024Article
- Identification of immune associated potential molecular targets in proliferative diabetic retinopathy.BMC ophthalmology · 2023Article
- Wnt Signaling in Inner Blood-Retinal Barrier Maintenance.International journal of molecular sciences · 2021Review
- Pharmacokinetics of the Urokinase Receptor-Derived Peptide UPARANT After Single and Multiple Doses Administration in Rats.European journal of drug metabolism and pharmacokinetics · 2021Article
- Gaining insight on mitigation of rubeosis iridis by UPARANT in a mouse model associated with proliferative retinopathy.Journal of molecular medicine (Berlin, Germany) · 2020Article
- COVID-19 and pneumonia: a role for the uPA/uPAR system.Drug discovery today · 2020Review
- Article
- RBP3: a possible prognostic marker and therapeutic target in diabetic retinopathy.Annals of translational medicine · 2019Article
- UPARANT is an effective antiangiogenic agent in a mouse model of rubeosis iridis.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Review
- The urokinase-type plasminogen activator system as drug target in retinitis pigmentosa: New pre-clinical evidence in the rd10 mouse model.Journal of cellular and molecular medicine · 2019Article
- Inhibiting the urokinase-type plasminogen activator receptor system recovers STZ-induced diabetic nephropathy.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spontaneously diabetic Torii (SDT) rat is of increasing preclinical interest because of its similarities to human type 2 diabetic retinopathy (DR). The system formed by urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is a player in blood-retinal barrier (BRB) breakdown in DR. Here, we investigated whether in SDT rats, preventive administration of UPARANT, an inhibitor of the uPAR pathway, counteracts the retinal impairment in response to chronic hyperglycemia. Electroretinogram (ERG) monitoring was followed over time. Fluorescein-dextran microscopy, CD31 immunohistochemistry, quantitative PCR, ELISA, Evans blue perfusion, and Western blot were also used. UPARANT prevented ERG dysfunction, upregulation of vascular endothelial growth factor and fibroblast growth factor-2, BRB leakage, gliosis, and retinal cell death. The mechanisms underlying UPARANT benefits were studied comparing them with the acute streptozotocin (STZ) model in which UPARANT is known to inhibit DR signs. In SDT rats, but not in the STZ model, UPARANT downregulated the expression of uPAR and its membrane partners. In both models, UPARANT reduced the levels of transcription factors coupled to inflammation or inflammatory factors themselves. These findings may help to establish the uPAR system as putative target for the development of novel drugs that may prevent type 2 DR.
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