ArticleThe American journal of pathology2016
Adeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Mice.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 54 citations in OpenAlex.
- Emerging innovations in ophthalmic drug delivery for diabetic retinopathy: a translational perspective.Drug delivery and translational research · 2026Review
- Hyperglycemia-Induced Endothelial Dysfunction: From Classical Pathogenetic Mechanisms to Emerging Insights into ACE2 Protective Action.International journal of molecular sciences · 2026Review
- Bibliometric and visual analysis of ACE2/Ang 1-7/MasR axis in diabetes and its microvascular complications from 2000 to 2023.Heliyon · 2024Article
- AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?Expert reviews in molecular medicine · 2024Review
- AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Sustained ACE2 Expression by Probiotic Improves Integrity of Intestinal Lymphatics and Retinopathy in Type 1 Diabetic Model.Journal of clinical medicine · 2023Article
- Maintenance of Enteral ACE2 Prevents Diabetic Retinopathy in Type 1 Diabetes.Circulation research · 2023Article
- Experiment-Based Interventions to Diabetic Retinopathy: Present and Advances.International journal of molecular sciences · 2022Review
- The Retinal Renin-Angiotensin-Aldosterone System: Implications for Glaucoma.Antioxidants (Basel, Switzerland) · 2022Article
- Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice.Science advances · 2022Article
- Gut Microbiota and Complications of Type-2 Diabetes.Nutrients · 2021Review
- Proline metabolism and transport in retinal health and disease.Amino acids · 2021Review
- A Review on Mesenchymal Stem Cells for Treatment of Retinal Diseases.Stem cell reviews and reports · 2021Review
- Angiotensin-converting enzyme 2 and kidney diseases in the era of coronavirus disease 2019.The Korean journal of internal medicine · 2021Review
- Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.Journal of vascular research · 2021Review
- Angiotensin-(1-7) Expressed From Lactobacillus Bacteria Protect Diabetic Retina in Mice.Translational vision science & technology · 2020Article
- The Gut-Eye Axis: Lessons Learned from Murine Models.Ophthalmology and therapy · 2020Review
- Review
- Eicosanoids and Oxidative Stress in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2020Review
- A novel interaction between soluble epoxide hydrolase and the AT1 receptor in retinal microvascular damage.Prostaglandins & other lipid mediators · 2020Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Angiotensin-converting enzyme (ACE)-2 is the primary enzyme of the vasoprotective axis of the renin angiotensin system that regulates the classic renin angiotensin system axis. We aimed to determine whether local retinal overexpression of adenoassociated virus (AAV)-ACE2 prevents or reverses diabetic retinopathy. Green fluorescent protein (GFP)-chimeric mice were generated to distinguish resident (retinal) from infiltrating bone marrow-derived inflammatory cells and were made diabetic using streptozotocin injections. Retinal digestion using trypsin was performed and acellular capillaries enumerated. Capillary occlusion by GFP(+) cells was used to measure leukostasis. Overexpression of ACE2 prevented (prevention cohort: untreated diabetic, 11.3 ± 1.4; ACE2 diabetic, 6.4 ± 0.9 per mm(2)) and partially reversed (reversal cohort: untreated diabetic, 15.7 ± 1.9; ACE2 diabetic, 6.5 ± 1.2 per mm(2)) the diabetes-associated increase of acellular capillaries and the increase of infiltrating inflammatory cells into the retina (F4/80(+)) (prevention cohort: untreated diabetic, 24.2 ± 6.7; ACE2 diabetic, 2.5 ± 1.6 per mm(2); reversal cohort: untreated diabetic, 56.8 ± 5.2; ACE2 diabetic, 5.6 ± 2.3 per mm(2)). In both study cohorts, intracapillary bone marrow-derived cells, indicative of leukostasis, were only observed in diabetic animals receiving control AAV injections. These results indicate that diabetic retinopathy, and possibly other diabetic microvascular complications, can be prevented and reversed by locally restoring the balance between the classic and vasoprotective renin angiotensin system.
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Registered trials
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