Soluble and membrane-bound adenylate kinase and nucleotidases augment ATP-mediated inflammation in diabetic retinopathy eyes with vitreous hemorrhage

• DOI: 10.1007/s00109-018-01734-0
• Publication Date: 2019-01-08T10:52:04Z
• Authors: Julian Zeiner; Sirpa Loukovaara; Karolina Losenkova; Mariachiara Zucca...; Ani M. Korhonen; Kaisa Lehti; Anu Kauppinen; Kai Kaarniranta; Christa E. Müller; Sirpa Jalkanen; Gennady G. Yegutkin
• Keywords: 5'-nucleotidase; Nucleotidase; Purinergic Signalling

ATP and adenosine are important signaling molecules involved in vascular remodeling, retinal function, neurovascular coupling the eye. Current knowledge on enzymatic pathways governing duration magnitude of ocular purinergic is incompletely understood. By employing sensitive analytical assays, this study dissected purine homeostasis as a complex coordinated network. Along with previously characterized ecto-5′-nucleotidase/CD73 adenylate kinase activities, other enzymes have been identified vitreous fluids, including nucleoside triphosphate diphosphohydrolase (NTPDase), deaminase, alkaline phosphatase. Strikingly, activities soluble kinase, ecto-5′-nucleotidase/CD73, phosphatase, well intravitreal concentrations ADP, were concurrently upregulated patients suffering from diabetic retinopathy (DR) non-clearing hemorrhage (VH), when compared to DR eyes without VH control operated due macular hole or pucker. Additional histochemical analysis revealed selective distribution key ecto-nucleotidases (NTPDase1/CD39, NTPDase2, phosphatase) human sensory neuroretina optic nerve head, also pathological neofibrovascular tissues surgically excised advanced proliferative DR. Collectively, these data provide evidence for specific hemorrhage-related shifts generation anti-inflammatory towards pro-inflammatory pro-angiogenic ATP-regenerating phenotype. In future, identifying exact mechanisms by which broad spectrum membrane-bound coordinately regulates levels further translation purine-converting potential therapeutic targets treatment vitreoretinal diseases will be an area intense interest.