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Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7

Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7

Authors :
Alan W. Stitt
Mei Chen
Kevin Harkin
Josy Augustine
Ronan Cunning
Heping Xu
Sofia Pavlou
Xu, Heping [0000-0003-4000-931X]
Chen, Mei [0000-0001-5661-1386]
Apollo - University of Cambridge Repository
Source :
International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 20, Iss 9, p 2101 (2019), Pavlou, S, Augustine, J, Cunning, R, Harkin, K, Stitt, A W, Xu, H & Chen, M 2019, ' Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7 ', International journal of molecular sciences, vol. 20, no. 9, 2101 . https://doi.org/10.3390/ijms20092101, Volume 20, Issue 9
Publication Year :
2019
Publisher :
MDPI AG, 2019.

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.

Details

Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 20, Iss 9, p 2101 (2019), Pavlou, S, Augustine, J, Cunning, R, Harkin, K, Stitt, A W, Xu, H & Chen, M 2019, ' Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7 ', International journal of molecular sciences, vol. 20, no. 9, 2101 . https://doi.org/10.3390/ijms20092101, Volume 20, Issue 9
Accession number :
edsair.doi.dedup.....357ba960fd2f49e9e38141994c9c641f
Full Text :
https://doi.org/10.17863/cam.41938