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Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7

Sofia Pavlou1, Josy Augustine2, Rónán Cunning3

  • 1Centre for Experimental Medicine, School of Medicine, Dentistry & Biomedical Science, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. s.pavlou@qub.ac.uk.

International Journal of Molecular Sciences
|May 1, 2019
PubMed

Insights

Lamivudine (3TC), a P2rx7 inhibitor, shows promise in treating diabetic retinopathy by protecting retinal neurons and blood vessels. This new treatment may prevent early-stage diabetic eye disease progression.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Pharmacology

Background:

  • Diabetic retinopathy involves retinal vascular and neuronal damage.
  • Neuroglial network defects may precede vascular lesions in diabetic retinopathy.
  • Targeting early neurodegeneration could prevent diabetic retinopathy progression.

Purpose of the Study:

  • To investigate the therapeutic potential of lamivudine (3TC) in a mouse model of diabetic retinopathy.
  • To determine if 3TC, a P2rx7 inhibitor, can attenuate both neuronal and vascular pathology.

Main Methods:

  • Assessed P2rx7 expression in diabetic mouse retinas.
  • Evaluated the effect of 3TC treatment on retinal vascular and neuronal integrity.
  • Measured electroretinogram (ERG) parameters (a- and b-wave, oscillatory potentials).
  • Quantified GABAergic amacrine cells and synaptophysin-positive areas.

Main Results:

  • P2rx7 expression was elevated in diabetic mouse retinas.
  • 3TC treatment protected against acellular capillary formation in diabetic mice.
  • 3TC preserved neuroglial function, indicated by improved ERG amplitudes.
  • 3TC treatment increased the number of GABAergic amacrine cells and synaptophysin-positive area.

Conclusions:

  • Lamivudine (3TC) demonstrates therapeutic potential for diabetic retinopathy.
  • 3TC effectively targets both neuronal and vascular pathologies associated with diabetes.
  • Inhibiting P2rx7 with 3TC may offer a novel treatment strategy for early diabetic retinopathy.
Keywords:
3TCP2rx7diabetic retinopathyretinal function

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