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Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pavlou, Sofia 
Augustine, Josy 
Cunning, Rónán 
Harkin, Kevin 
Stitt, Alan W 

Abstract

Retinal vascular and neuronal degeneration are established pathological features of diabetic retinopathy. Data suggest that defects in the neuroglial network precede the clinically recognisable vascular lesions in the retina. Therefore, new treatments that target early-onset neurodegeneration would be expected to have great value in preventing the early stages of diabetic retinopathy. Here, we show that the nucleoside reverse transcriptase inhibitor lamivudine (3TC), a newly discovered P2rx7 inhibitor, can attenuate progression of both neuronal and vascular pathology in diabetic retinopathy. We found that the expression of P2rx7 was increased in the murine retina as early as one month following diabetes induction. Compared to non-diabetic controls, diabetic mice treated with 3TC were protected against the formation of acellular capillaries in the retina. This occurred concomitantly with a maintenance in neuroglial function, as shown by improved a- and b-wave amplitude, as well as oscillatory potentials. An improvement in the number of GABAergic amacrine cells and the synaptophysin-positive area was also observed in the inner retina of 3TC-treated diabetic mice. Our data suggest that 3TC has therapeutic potential since it can target both neuronal and vascular defects caused by diabetes.

Description

Keywords

3TC, P2rx7, diabetic retinopathy, retinal function, Animals, Biomarkers, Diabetes Mellitus, Experimental, Diabetic Retinopathy, Electroretinography, Fluorescent Antibody Technique, Gene Expression, Immunohistochemistry, Lamivudine, Male, Mice, Purinergic P2X Receptor Antagonists, Receptors, Purinergic P2X7, Retinal Neurons, Retinal Vessels, Tomography, Optical Coherence

Journal Title

Int J Mol Sci

Conference Name

Journal ISSN

1661-6596
1422-0067

Volume Title

20

Publisher

MDPI AG