Abstract
Purpose :
Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. The aim of the present study was to investigate the protection of P2X7 receptor ligands on high glucose-induced human retinal pericytes.
Methods :
JNJ47965567 (JNJ), previously identified as the hit compound by molecular modeling study, was used as P2X7 receptor antagonist; 2',3'-O-(4-benzoyl-benzoyl)-ATP (BzATP) was used as P2X7 receptor agonist. Human retinal pericytes were exposed to high glucose (25 mM, 48 h) to mimic an in vitro model of early diabetic retinopathy. Cell viability, IL-1β and LDH levels were assessed with or without P2X7 receptor ligands treatment.
Results :
High glucose caused a significant (p<0.001) release of IL-1β and LDH as well as a loss of cell viability. Stimulation of P2X7 receptor by the selective agonist BzATP (100 µM) induced cell damage and IL-1b release comparable to those induced by high glucose. Treatment with JNJ was able to significantly (p<0.001) protect, in a dose-depending manner, pericytes from glucose or BzATP damage in terms of cell viability, IL-1β and LDH release.
Conclusions :
Overall, the present findings suggest that the P2X7 receptor is a potential pharmacological target to protect retinal pericytes from high glucose damage.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.