Extracellular ATP accelerates photoreceptor cell death via ligation of P2X7 receptor in retinal detachment

Abstract

Purpose: Extracellular ATP is released from damaged tissue and acts on P2X purinergic receptor. Recently, ATP has been known as a damage-associated molecular pattern (DAMP) molecule which can participate neurodegenerative processes via induction of specific inflammatory responses. We investigated the role of extracellular ATP as a DAMP molecule in an animal model of retinal detachment.

Methods: We compared ATP levels of vitreous samples from patients with rhegmatogenous retinal detachment (RRD) to those of macular hole (MH) or epi-retinal membrane (ERM). The ATP concentrations were quantified by luciferase assay. We tested whether extracellular ATP is involved in neuroinflammation by means of primary retinal cell cultures and a rodent model of retinal detachment. We also examined the effect of pharmacological blockade or genetic deficiency of P2X7 on photoreceptor death caused by retinal detachment.

Results: The ATP levels in vitreous samples of patients with RRD were significantly higher than those of MH or ERM. Extracellular ATP induced a significant decline of photoreceptor viability in primary retinal cell cultures. Inflammatory cytokines as well as TUNEL-detectable photoreceptor apoptosis was significantly reduced by pharmacological blockade or genetic deficiency of P2X7 in retinal detachment.

Conclusions: Extracellular ATP accelerates inflammatory responses and photoreceptor apoptosis in retinal detachment. Pharmacological P2X7 blockade may provide potential therapeutic effects in retinal detachment.

Keywords: 697 retinal detachment • 449 cell survival • 557 inflammation