ArticleMolecular vision2007
Reduction of experimental diabetic vascular leakage by delivery of angiostatin with a recombinant adeno-associated virus vector.
Article in Molecular vision, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Experiment-Based Interventions to Diabetic Retinopathy: Present and Advances.International journal of molecular sciences · 2022Review
- The role of Müller cell glucocorticoid signaling in diabetic retinopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2020Review
- Adeno-Associated Viral Vector 2 and 9 Transduction Is Enhanced in Streptozotocin-Induced Diabetic Mouse Retina.Molecular therapy. Methods & clinical development · 2019Article
- Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats.International journal of nanomedicine · 2019Article
- Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies.Expert opinion on biological therapy · 2018Review
- Therapeutic Effects of a Novel Phenylphthalimide Analog for Corneal Neovascularization and Retinal Vascular Leakage.Investigative ophthalmology & visual science · 2018Article
- Dual contribution of TRPV4 antagonism in the regulatory effect of vasoinhibins on blood-retinal barrier permeability: diabetic milieu makes a difference.Scientific reports · 2017Article
- Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Reduce Reactive Gliosis and Improve Angiostatin Levels in Retina of Diabetic Rats.Neurochemical research · 2016Article
- Diabetes enhances the efficacy of AAV2 vectors in the retina: therapeutic effect of AAV2 encoding vasoinhibin and soluble VEGF receptor 1.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- Matrix metalloproteinase 9-mediated intracerebral hemorrhage induced by cerebral amyloid angiopathy.Neurobiology of aging · 2015Article
- Retinal Gene Therapy: Current Progress and Future Prospects.Expert review of ophthalmology · 2015Article
- Identification of a novel inhibitor of the canonical Wnt pathway.Molecular and cellular biology · 2011Article
- Agents that bind annexin A2 suppress ocular neovascularization.Journal of cellular physiology · 2010Article
- Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV.Gene therapy · 2009Article
- Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation.The Journal of clinical investigation · 2008Article
- A Hypothesis Concerning the Biphasic Dose-response of Tumors to Angiostatin and Endostatin.Dose-response : a publication of International Hormesis SocietyArticle
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo evaluate the efficacy of recombinant adeno-associated virus (rAAV) vector expressing mouse angiostatin (Kringle domains 1 to 4) in reducing retinal vascular leakage in an experimental diabetic rat model.
methodsrAAV-angiostatin was delivered by intravitreal injection to the right eyes of Sprague-Dawley rats. As a control, the contralateral eye received an intravitreal injection of rAAV-lacZ. Gene delivery was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). Diabetes was induced by intravenous injection of streptozotocin (STZ). Vascular permeability changes were evaluated by extravascular albumin accumulation and leakage of intravenous-injected fluorescein isothiocynate-bovine serum albumin (FITC-BSA). Effects of rAAV-angiostatin on expression of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), occludin, and phospho-p42/p44 MAP kinase in retina tissue were analyzed by western blotting.
resultsThe rAAV-angiostatin injections led to sustained angiostatin gene expression in retina as confirmed by RT-PCR, and reduced extravascular albumin accumulation in STZ-induced diabetic retina. Further, rAAV-angiostatin significantly decreased intravascularly injected FITC-BSA leakage at 5 days (p=0.001), 10 days (p<0.001), and 15 days (p=0.001) after STZ-induced diabetes, as compared to the control eyes receiving rAAV-lacZ. Expression of VEGF and phosphorylation of p42/p44 MAP kinase in retina was reduced by rAAV-angiostatin at day 1 (p=0.043 for both VEGF and phospho-p42/p44 MAP kinase) after STZ-induced diabetes compared with rAAV-lacZ eyes. rAAV-angiostatin reduced retinal occludin loss at 10 days after STZ-induced diabetes (n=5, p=0.041). There was no significant difference in retinal PEDF expression between eyes injected with rAAV-angiostatin and rAAV-lacZ.
conclusionsIntravitreal delivery of rAAV-angiostatin reduces vascular leakage in an STZ-induced diabetic model. This effect is associated with a reduction in the retinal occludin loss induced by diabetes and downregulation of retinal VEGF and phosphor-p42/p44 MAP kinase expression. This gene transfer approach may reduce diabetic macular edema, providing protection in diabetic patients at risk for macular edema.
Indexed as
Identifiers
17293777PMC2533034W1868835986What 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.