P2X₇Receptor Activation Mediates Retinal Ganglion Cell Death in a Human Retina Model of Ischemic Neurodegeneration

Abstract

These studies demonstrated that stimulation of the P2X7R can mediate RGC death and that this mechanism plays a role in ischemia-induced neurodegeneration in the human retina.

Purinergic Signaling and Blood Vessels in Health and Disease

“…It has been suggested that suppressing neuronal necrosis using ATP-liposomes in ischemiareperfusion-challenged neuronal tissues could promote a neuroprotective environment and reduce tissue damage (Dvoriantchikova et al, 2010). P2X 7 receptor activation causes retinal ganglion cell death in a human retina model of ischemic neurodegeneration (Niyadurupola et al, 2013).…”

Cellular and Molecular Mechanisms of Retinal Ganglion Cell Death in Hypoxic-Ischemic Injuries

“…While a short term stimulation of P2X 7 receptors induces physiological calcium response, prolonged stimulation is shown to mediate RGC death [134]. Under hypoxic/ ischemic conditions, activation of P2X receptors, specifically the P2X 7 receptor, has been reported to cause death of RGCs [134,135] by enhancing intracellular calcium levels. However, inhibition of P2X 7 receptor prevented the death of RGCs following ischemic insult [135].…”

“…Under hypoxic/ ischemic conditions, activation of P2X receptors, specifically the P2X 7 receptor, has been reported to cause death of RGCs [134,135] by enhancing intracellular calcium levels. However, inhibition of P2X 7 receptor prevented the death of RGCs following ischemic insult [135]. Taken together these studies provide compelling evidence for the involvement of P2X 7 in RGCs death.…”

Fluorescent dyes as a reliable tool in P2X7 receptor-associated pore studies

“…These are the main probes used to assess the pore phenomenon. Over the years, it has been shown that both physiological and pathophysiological events such as osmoregulation (Morales et al 2007;Nedungadi et al 2012), hypoxia/ schemic conditions (Sugiyama et al 2010) and cell death (Burnstock 2002;Niyadurupola et al 2013) are responsible for these phenomena, suggesting critical roles for poreassociated proteins. We highlight in this work the P2X7 receptor, which has been related to critical events such as pain (Donnelly-Roberts and Jarvis 2007; Cotrina and Nedergaard 2009;Skaper et al 2010;Nörenberg et al 2011;Alves et al 2013), cancer (Raffaghello et al 2006;Feng et al 2006;Adinolfi et al 2012a, b;Haanes et al 2012;Bian et al 2013) and cell death (Burnstock 2002;Niyadurupola et al 2013).…”

“…Over the years, it has been shown that both physiological and pathophysiological events such as osmoregulation (Morales et al 2007;Nedungadi et al 2012), hypoxia/ schemic conditions (Sugiyama et al 2010) and cell death (Burnstock 2002;Niyadurupola et al 2013) are responsible for these phenomena, suggesting critical roles for poreassociated proteins. We highlight in this work the P2X7 receptor, which has been related to critical events such as pain (Donnelly-Roberts and Jarvis 2007; Cotrina and Nedergaard 2009;Skaper et al 2010;Nörenberg et al 2011;Alves et al 2013), cancer (Raffaghello et al 2006;Feng et al 2006;Adinolfi et al 2012a, b;Haanes et al 2012;Bian et al 2013) and cell death (Burnstock 2002;Niyadurupola et al 2013). Moreover, along with tumor establishment (Baricordi et al 1999;Amoroso et al 2012;Thompson et al 2012;Adinolfi et al 2012b;Rigato et al 2012;Hattori et al 2012), P2X7R plays important roles in infectious diseases like tuberculosis (Sikora et al 1999;Kusner and Adams 2000;Smith et al 2001;FrancoMartínez et al 2006;Fernando et al 2007;Marques-daSilva et al 2011;Wiley et al 2011;Ghiadoni et al 2013) and leishmaniosis (Chaves et al 2009;Marques-da-Silva et al 2011).…”