ArticleDiabetes2015
Plasma Kallikrein-Kinin System as a VEGF-Independent Mediator of Diabetic Macular Edema.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 88 citations in OpenAlex.
- Deep Proteomic Analysis With Machine Learning Identifies Aqueous Humor Biomarkers of ADAMTSL4-associated Congenital Ectopia Lentis.Investigative ophthalmology & visual science · 2026Article
- Pharmacological Treatment for Diabetic Macular Edema: A 2025 Update on Durability and Multi-Target Therapies.Drug design, development and therapy · 2026Review
- Proteomics analysis of aqueous and vitreous humor in uveitis: a systematic literature review.Clinical proteomics · 2025Review
- Stage-dependent proteomic alterations in aqueous humor of diabetic retinopathy patients based on data-independent acquisition and parallel reaction monitoring.Journal of translational medicine · 2025Article
- Diabetic macular edema (DME): dissecting pathogenesis, prognostication, diagnostic modalities along with current and futuristic therapeutic insights.International journal of retina and vitreous · 2024Review
- Increased Prolylcarboxypeptidase Expression Can Serve as a Biomarker of Senescence in Culture.Molecules (Basel, Switzerland) · 2024Article
- Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system.Journal of translational medicine · 2024Review
- 6-(Arylaminomethyl) Isoquinolines as Enzyme Inhibitors and Their Preparation: A Patent Highlight of Factor XIIa Inhibitors.Cardiovascular & hematological agents in medicinal chemistry · 2023Article
- Vitreous humor proteome: unraveling the molecular mechanisms underlying proliferative and neovascular vitreoretinal diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Spleen Tyrosine Kinase Contributes to Müller Glial Expression of Proangiogenic Cytokines in Diabetes.Investigative ophthalmology & visual science · 2022Article
- Review
- Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: a systematic review and meta-analysis.Eye (London, England) · 2022Review
- Molecules related to diabetic retinopathy in the vitreous and involved pathways.International journal of ophthalmology · 2022Review
- Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy.Current diabetes reviews · 2022Article
- Neuroinflammation and neurodegeneration in diabetic retinopathy.Frontiers in aging neuroscience · 2022Review
- 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
- [Bradykinin and angiotensin-converting enzyme in serum of patients with diabetic retinopathy and the prognosis of diabetic macular edema development (pilot study)].Problemy endokrinologii · 2021Article
- AMP-activated protein kinase is a key regulator of acute neurovascular permeability.Journal of cell science · 2021Article
Corrections and comments
- Commented on by
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
This study characterizes the kallikrein-kinin system in vitreous from individuals with diabetic macular edema (DME) and examines mechanisms contributing to retinal thickening and retinal vascular permeability (RVP). Plasma prekallikrein (PPK) and plasma kallikrein (PKal) were increased twofold and 11.0-fold (both P < 0.0001), respectively, in vitreous from subjects with DME compared with those with a macular hole (MH). While the vascular endothelial growth factor (VEGF) level was also increased in DME vitreous, PKal and VEGF concentrations do not correlate (r = 0.266, P = 0.112). Using mass spectrometry-based proteomics, we identified 167 vitreous proteins, including 30 that were increased in DME (fourfold or more, P < 0.001 vs. MH). The majority of proteins associated with DME displayed a higher correlation with PPK than with VEGF concentrations. DME vitreous containing relatively high levels of PKal and low VEGF induced RVP when injected into the vitreous of diabetic rats, a response blocked by bradykinin receptor antagonism but not by bevacizumab. Bradykinin-induced retinal thickening in mice was not affected by blockade of VEGF receptor 2. Diabetes-induced RVP was decreased by up to 78% (P < 0.001) in Klkb1 (PPK)-deficient mice compared with wild-type controls. B2- and B1 receptor-induced RVP in diabetic mice was blocked by endothelial nitric oxide synthase (NOS) and inducible NOS deficiency, respectively. These findings implicate the PKal pathway as a VEGF-independent mediator of DME.
Indexed as
Identifiers
What OpenQuestion holds
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.