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13.04.2019 | Original Article

Pharmacological blockade of the P2X7 receptor reverses retinal damage in a rat model of type 1 diabetes

verfasst von: Carmen Clapp, Nundehui Diaz-Lezama, Elva Adan-Castro, Gabriela Ramirez-Hernandez, Bibiana Moreno-Carranza, Alba Clara Sarti, Simonetta Falzoni, Anna Solini, Francesco Di Virgilio

Erschienen in: Acta Diabetologica | Ausgabe 9/2019

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Abstract

Aims

Retinopathy is a leading cause of vision impairment in diabetes. Its pathogenesis involves inflammation, pathological angiogenesis, neuronal and glial dysfunction. The purinergic P2X7 receptor (P2X7R) has a leading role in inflammation and angiogenesis. Potent and selective P2X7R blockers have been synthesized and tested in Phase I/II clinical studies. We hypothesize that P2X7R blockade will ameliorate diabetes-related pathological retinal changes.

Methods

Streptozotocin (STZ)-treated rats were intraperitoneally inoculated with either of two small molecule P2X7R receptor inhibitors, A740003 and AZ10606120, and after blood glucose levels increased to above 400 mg/dL, retinae were analyzed for P2X7R expression, vascular permeability, VEGF, and IL-6 expression.

Results

STZ administration caused a near fourfold increase in blood glucose, a large increase in retinal microvasculature permeability, as well as in retinal P2X7R, VEGF, and IL-6 expression. P2X7R blockade fully reversed retinal vascular permeability increase, VEGF accumulation, and IL-6 expression, with no effect on blood glucose.

Conclusion

P2X7R blockade might be promising strategy for the treatment of microvascular changes observed in the early phases of diabetic retinopathy.

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Titel: Pharmacological blockade of the P2X7 receptor reverses retinal damage in a rat model of type 1 diabetes
verfasst von: Carmen Clapp
Nundehui Diaz-Lezama
Elva Adan-Castro
Gabriela Ramirez-Hernandez
Bibiana Moreno-Carranza
Alba Clara Sarti
Simonetta Falzoni
Anna Solini
Francesco Di Virgilio
Publikationsdatum: 13.04.2019
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe 9/2019
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-019-01343-4

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Pharmacological blockade of the P2X7 receptor reverses retinal damage in a rat model of type 1 diabetes

Abstract