ArticleJournal of molecular medicine (Berlin, Germany)2019
Soluble and membrane-bound adenylate kinase and nucleotidases augment ATP-mediated inflammation in diabetic retinopathy eyes with vitreous hemorrhage.
Article in Journal of molecular medicine (Berlin, Germany), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.Frontiers in cell and developmental biology · 2026Review
- Purinergic enzymes on extracellular vesicles: immune modulation on the go.Frontiers in immunology · 2024Review
- Protein-metabolite association studies identify novel proteomic determinants of metabolite levels in human plasma.Cell metabolism · 2023Article
- Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy.Frontiers in molecular neuroscience · 2023Review
- ATP and Adenosine Metabolism in Cancer: Exploitation for Therapeutic Gain.Pharmacological reviews · 2022Review
- Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders.International journal of molecular sciences · 2022Review
- CD73 controls ocular adenosine levels and protects retina from light-induced phototoxicity.Cellular and molecular life sciences : CMLS · 2022Article
- Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies.International journal of molecular sciences · 2021Article
- In Search of a Role for Extracellular Purine Enzymes in Bone Function.Biomolecules · 2021Review
- RNA sequencing reveals BMP4 as a basis for the dual-target treatment of diabetic retinopathy.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Review
- Fluorescent Probes for Ecto-5'-nucleotidase (CD73).ACS medicinal chemistry letters · 2020Article
- Adenosine Metabolism: Emerging Concepts for Cancer Therapy.Cancer cell · 2019Review
- Generation and Function of Non-cell-bound CD73 in Inflammation.Frontiers in immunology · 2019Review
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATP and adenosine are important signaling molecules involved in vascular remodeling, retinal function, and neurovascular coupling in the eye. Current knowledge on enzymatic pathways governing the duration and magnitude of ocular purinergic signaling is incompletely understood. By employing sensitive analytical assays, this study dissected ocular purine homeostasis as a complex and coordinated network. Along with previously characterized ecto-5'-nucleotidase/CD73 and adenylate kinase activities, other enzymes have been identified in vitreous fluids, including nucleoside triphosphate diphosphohydrolase (NTPDase), adenosine deaminase, and alkaline phosphatase. Strikingly, activities of soluble adenylate kinase, adenosine deaminase, ecto-5'-nucleotidase/CD73, and alkaline phosphatase, as well as intravitreal concentrations of ATP and ADP, were concurrently upregulated in patients suffering from diabetic retinopathy (DR) with non-clearing vitreous hemorrhage (VH), when compared to DR eyes without VH and control eyes operated due to macular hole or pucker. Additional histochemical analysis revealed selective distribution of key ecto-nucleotidases (NTPDase1/CD39, NTPDase2, ecto-5'-nucleotidase/CD73, and alkaline phosphatase) in the human sensory neuroretina and optic nerve head, and also in pathological neofibrovascular tissues surgically excised from patients with advanced proliferative DR. Collectively, these data provide evidence for specific hemorrhage-related shifts in purine homeostasis in DR eyes from the generation of anti-inflammatory adenosine towards a pro-inflammatory and pro-angiogenic ATP-regenerating phenotype. In the future, identifying the exact mechanisms by which a broad spectrum of soluble and membrane-bound enzymes coordinately regulates ocular purine levels and the further translation of purine-converting enzymes as potential therapeutic targets in the treatment of proliferative DR and other vitreoretinal diseases will be an area of intense interest. KEY MESSAGES: NTPDase, alkaline phosphatase, and adenosine deaminase circulate in human vitreous. Purinergic enzymes are up-regulated in diabetic eyes with vitreous hemorrhage. Soluble adenylate kinase maintains high ATP levels in diabetic retinopathy eyes. Ecto-nucleotidases are co-expressed in the human retina and optic nerve head. Alkaline phosphatase is expressed on neovascular tissues excised from diabetic eyes.
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