ArticleThe Journal of clinical investigation2008
Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03161652 (Clinical Trial to Evaluate the Safety and Efficacy of Levosulpiride to Improve Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema.), which is not on this map. Cited by 42 papers.
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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.
Clinical Trial to Evaluate the Safety and Efficacy of Levosulpiride to Improve Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema.
Who cites it
42 citing papers in PubMed, 82 citations in OpenAlex.
- Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial.Eye (London, England) · 2024Trial
- Therapeutic potential of prolactin-releasing anti-dopaminergic agents in experimental diabetic retinopathy model.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Cardiovascular Safety of VIAN-c4551, an Antiangiogenic Peptide Derived From Vasoinhibin.Drug development research · 2025Article
- Topical ophthalmic administration of the antiangiogenic peptide VIAN-c4551 protects against experimental diabetic macular edema.Scientific reports · 2025Article
- The antiangiogenic peptide VIAN-c4551 inhibits lung melanoma metastasis in mice by reducing pulmonary vascular permeability.PloS one · 2025Article
- Prolactin: structure, receptors, and functions.Reviews in endocrine & metabolic disorders · 2024Review
- The effects of probiotics supplements on metabolic indices and clinical signs in patients with diabetic retinopathy, a randomized double blind clinical trial.Journal of diabetes and metabolic disorders · 2024Article
- Prolactin Expression in the Baboon (Animals : an open access journal from MDPI · 2022Article
- The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide.Angiogenesis · 2022Article
- Prolactin and vasoinhibin are endogenous players in diabetic retinopathy revisited.Frontiers in endocrinology · 2022Review
- Gliquidone improves retinal injury to relieve diabetic retinopathy via regulation of SIRT1/Notch1 pathway.BMC ophthalmology · 2021Article
- Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis.Cells · 2021Review
- Vasoinhibin reduces joint inflammation, bone loss, and the angiogenesis and vasopermeability of the pannus in murine antigen-induced arthritis.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Circular RNA-ZNF532 regulates diabetes-induced retinal pericyte degeneration and vascular dysfunction.The Journal of clinical investigation · 2020Article
- Neuroprotective Peptides in Retinal Disease.Journal of clinical medicine · 2019Review
- Differential activity of 16K rat prolactin in different organic systems.Animal cells and systems · 2019Article
- Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy.Frontiers in neuroscience · 2019Review
- Regulator of Angiogenesis and Vascular Function: A 2019 Update of the Vasoinhibin Nomenclature.Frontiers in endocrinology · 2019Article
- Vasoinhibin comprises a three-helix bundle and its antiangiogenic domain is located within the first 79 residues.Scientific reports · 2018Article
- Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema.Frontiers in endocrinology · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. Here, we demonstrate what we believe to be a novel function of vasoinhibins as inhibitors of the increased retinal vasopermeability associated with diabetic retinopathy. Vasoinhibins inhibited VEGF-induced vasopermeability in bovine aortic and rat retinal capillary endothelial cells in vitro. In vivo, vasoinhibins blocked retinal vasopermeability in diabetic rats and in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy. Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. Moreover, intravitreous injection of okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on endothelial cell permeability and retinal vasopermeability. These results suggest that vasoinhibins have the potential to be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies.
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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.