Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

Show full item record



Permalink

http://hdl.handle.net/10138/232541

Citation

Loukovaara , S , Sandholm , J , Aalto , K , Liukkonen , J , Jalkanen , S & Yegutkin , G G 2017 , ' Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy ' Journal of Molecular Medicine , vol. 95 , no. 2 , pp. 193-204 . DOI: 10.1007/s00109-016-1472-6

Title: Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy
Author: Loukovaara, Sirpa; Sandholm, Jouko; Aalto, Kristiina; Liukkonen, Janne; Jalkanen, Sirpa; Yegutkin, Gennady G.
Contributor: University of Helsinki, Silmäklinikka
Date: 2017-02
Language: eng
Number of pages: 12
Belongs to series: Journal of Molecular Medicine
ISSN: 0946-2716
URI: http://hdl.handle.net/10138/232541
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.
Subject: Diabetic retinopathy
Vitreous fluid
ATP
ADP
Ecto-5 '-nucleotidase/CD73
Adenylate kinase-1
EXTRACELLULAR ATP
PHOSPHOTRANSFER REACTIONS
PHOTORECEPTOR PRECURSORS
RETINAL DEGENERATION
TRABECULAR MESHWORK
ENDOTHELIAL-CELLS
ADENYLATE KINASE
METABOLISM
ADENOSINE
DISEASE
1184 Genetics, developmental biology, physiology
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
Deregulation_of_ocular_nucleotide_homeostasis.pdf 3.001Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record