Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Loukovaara S, Sandholm J, Aalto K, Liukkonen J, Jalkanen S, Yegutkin GG
Publisher: SPRINGER
Publication year: 2017
Journal: Journal of Molecular Medicine
Journal acronym: J MOL MED
Volume number: 95
Issue number: 2
Start page: 193
End page: 204
Number of pages: 12
ISSN: 0946-2716


Abstract

Clear signaling roles for ATP and adenosine have been established in all tissues, including the eye. The magnitude of signaling responses is governed by networks of enzymes; however, little is known about the regulatory mechanisms of purinergic signaling in the eye. By employing thin-layer chromatographic assays with 3H-labeled substrates, this study aimed to evaluate the role of nucleotide homeostasis in the pathogenesis of vitreoretinal diseases in humans. We have identified soluble enzymes ecto-5'-nucleotidase/CD73, adenylate kinase-1, and nucleoside diphosphate kinase in the vitreous fluid that control active cycling between proinflammatory ATP and anti-inflammatory adenosine. Strikingly, patients with proliferative form of diabetic retinopathy (DR) had higher adenylate kinase activity and ATP concentration, when compared to non-proliferative DR eyes and non-diabetic controls operated for rhegmatogenous retinal detachment, macular hole, and pucker. The non-parametric correlation analysis revealed positive correlations between intravitreal adenylate kinase and concentrations of ATP, ADP, and other angiogenic (angiopoietins-1 and -2), profibrotic (transforming growth factor-similar to 1), and proteolytic (matrix metalloproteinase-9) factors but not erythropoietin and VEGF. Immunohistochemical staining of postmortem human retina additionally revealed selective expression of ecto-5'-nucleotidase/ CD73 on the rod-and-cone-containing photoreceptor cells. Collectively, these findings provide novel insights into the regulatory mechanisms that influence purinergic signaling in diseased eye and open up new possibilities in the development of enzyme-targeted therapeutic approaches for prevention and treatment of DR.


Keywords

Adenylate kinase-1, ADP, ATP, Ecto-5 '-nucleotidase/CD73, Vitreous fluid

Last updated on 2019-18-10 at 03:33