ArticleDiabetes2011
Plasma kallikrein mediates retinal vascular dysfunction and induces retinal thickening in diabetic rats.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 93 citations in OpenAlex.
- Review
- Pharmacological Treatment for Diabetic Macular Edema: A 2025 Update on Durability and Multi-Target Therapies.Drug design, development and therapy · 2026Review
- Recent Investigations on Pathogenesis, Biomarkers, Epigenetics, and Emerging Therapeutic Strategies to Modulate Multiple Signaling Pathways in Diabetic Retinopathy.Journal of ophthalmology · 2026Review
- Differential Effects of Retinol-Binding Protein 3 and Anti-VEGF Antibodies on Retinal Dysfunctions in Diabetic Retinopathy.Diabetes · 2025Article
- What's New in Ocular Drug Delivery: Advances in Suprachoroidal Injection since 2023.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The Complement System as a Therapeutic Target in Retinal Disease.Medicina (Kaunas, Lithuania) · 2024Review
- Tocotrienol-rich fraction reduces retinal inflammation and angiogenesis in rats with streptozotocin-induced diabetes.BMC complementary medicine and therapies · 2023Article
- Glycated albumin modulates the contact system with implications for the kallikrein-kinin and intrinsic coagulation systems.Journal of thrombosis and haemostasis : JTH · 2023Article
- Non-alcoholic fatty liver disease and liver secretome.Archives of pharmacal research · 2022Review
- Review
- Phase 1 Dose-Escalation Study of Plasma Kallikrein Inhibitor THR-149 for the Treatment of Diabetic Macular Edema.Translational vision science & technology · 2021Article
- Targeting Plasma Kallikrein With a Novel Bicyclic Peptide Inhibitor (THR-149) Reduces Retinal Thickening in a Diabetic Rat Model.Investigative ophthalmology & visual science · 2021Article
- Recent Advancements in the Medical Treatment of Diabetic Retinal Disease.International journal of molecular sciences · 2021Review
- Review
- Current understanding of the molecular and cellular pathology of diabetic retinopathy.Nature reviews. Endocrinology · 2021Review
- Evans blue staining to detect deep blood vessels in peripheral retina for observing retinal pathology in early-stage diabetic rats.International journal of ophthalmology · 2021Article
- Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group.Eye (London, England) · 2020Review
- The effects of anti-VEGF and kinin BBritish journal of pharmacology · 2020Article
- Investigational plasma kallikrein inhibitors for the treatment of diabetic macular edema: an expert assessment.Expert opinion on investigational drugs · 2020Review
- Complement, a Therapeutic Target in Diabetic Kidney Disease.Frontiers in medicine · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePlasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. RESEARCH DESIGN AND
methodsWe investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography.
resultsSystemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks' diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks' diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 ± 10 μm to 223 ± 13 μm) compared with nondiabetic rats (from 182 ± 8 μm to 193 ± 9 μm).
conclusionsThese results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening.
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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.