ArticleExperimental eye research2016
Dimethylarginine dimethylaminohydrolase-2 deficiency promotes vascular regeneration and attenuates pathological angiogenesis.
Article in Experimental eye research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Therapeutic Modulation of Nitric Oxide Pathways to Address Insulin Resistance in Cardiovascular-Kidney-Metabolic Syndrome.International journal of molecular sciences · 2026Review
- Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles.American journal of physiology. Renal physiology · 2024Article
- Transcriptional Comparison of Human and Murine Retinal Neovascularization.Investigative ophthalmology & visual science · 2023Article
- A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase.Nature communications · 2023Article
- Predicting late-stage age-related macular degeneration by integrating marginally weak SNPs in GWA studies.Frontiers in genetics · 2023Article
- Role of ADMA in the pathogenesis of microvascular complications in type 2 diabetes mellitus.Frontiers in endocrinology · 2023Review
- Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation.International journal of molecular sciences · 2022Article
- Immunosenescence in Choroidal Neovascularization (CNV)-Transcriptional Profiling of Naïve and CNV-Associated Retinal Myeloid Cells during Aging.International journal of molecular sciences · 2021Article
- The role of interferon regulatory factor 8 for retinal tissue homeostasis and development of choroidal neovascularisation.Journal of neuroinflammation · 2021Article
- Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity.Scientific reports · 2021Article
- ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis.Journal of clinical medicine · 2020Review
- Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature.Frontiers in oncology · 2020Review
- Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer.Frontiers in oncology · 2019Review
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Ischemia-induced angiogenesis is critical for tissue repair, but aberrant neovascularization in the retina causes severe sight impairment. Nitric oxide (NO) has been implicated in neovascular eye disease because of its pro-angiogenic properties in the retina. Nitric oxide production is inhibited endogenously by asymmetric dimethylarginines (ADMA and L-NMMA) which are metabolized by dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2. The aim of this study was to determine the roles of DDAH1, DDAH2, ADMA and L-NMMA in retinal ischemia-induced angiogenesis. First, DDAH1, DDAH2, ADMA and L-NMMA levels were determined in adult C57BL/6J mice. The results obtained revealed that DDAH1 was twofold increased in the retina compared to the brain and the choroid. DDAH2 expression was approximately 150 fold greater in retinal and 70 fold greater in choroidal tissue compared to brain tissue suggesting an important tissue-specific role for DDAH2 in the retina and choroid. ADMA and L-NMMA levels were similar in the retina and choroid under physiological conditions. Next, characterization of DDAH1(+/-) and DDAH2(-/-) deficient mice by in vivo fluorescein angiography, immunohistochemistry and electroretinography revealed normal neurovascular function compared with wildtype control mice. Finally, DDAH1(+/-) and DDAH2(-/-) deficient mice were studied in the oxygen-induced retinopathy (OIR) model, a model used to emulate retinal ischemia and neovascularization, and VEGF and ADMA levels were quantified by ELISA and liquid chromatography tandem mass spectrometry. In the OIR model, DDAH1(+/-) exhibited a similar phenotype compared to wildtype controls. DDAH2 deficiency, in contrast, resulted in elevated retinal ADMA which was associated with attenuated aberrant angiogenesis and improved vascular regeneration in a VEGF independent manner. Taken together this study suggests, that in retinal ischemia, DDAH2 deficiency elevates ADMA, promotes vascular regeneration and protects against aberrant angiogenesis. Therapeutic inhibition of DDAH2 may therefore offer a potential therapeutic strategy to protect sight by promoting retinal vascular regeneration and preventing pathological angiogenesis.
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