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Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7
Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7
- 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.
- Subjects :
- 0301 basic medicine
Male
Pathology
Fluorescent Antibody Technique
Gene Expression
P2rx7
Nucleoside Reverse Transcriptase Inhibitor
lcsh:Chemistry
chemistry.chemical_compound
Mice
0302 clinical medicine
Medicine
lcsh:QH301-705.5
Spectroscopy
retinal function
Neurodegeneration
General Medicine
Diabetic retinopathy
Immunohistochemistry
Computer Science Applications
medicine.anatomical_structure
Lamivudine
GABAergic
Tomography, Optical Coherence
Retinal Neurons
medicine.medical_specialty
Purinergic P2X Receptor Antagonists
Catalysis
Article
Diabetes Mellitus, Experimental
Inorganic Chemistry
03 medical and health sciences
SDG 3 - Good Health and Well-being
Diabetes mellitus
Electroretinography
Animals
Physical and Theoretical Chemistry
Molecular Biology
3TC
Retina
Diabetic Retinopathy
business.industry
Organic Chemistry
Retinal Vessels
Retinal
P2RX7
medicine.disease
030104 developmental biology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Receptors, Purinergic P2X7
business
030217 neurology & neurosurgery
Biomarkers
Subjects
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