Role of P2X7 receptors in the development of diabetic retinopathy

Abstract

The P2X₇ receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5’-triphosphate. A unique feature of the P2X₇ receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X₇-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X₇ receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X₇ receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X₇ receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation.

Keywords: P2X₇ receptor; Diabetic retinopathy; Vasotoxicity; Retinal microvessels; Interleukin-1β; Tumor necrosis factor-α

Core tip: This review summarizes the studies regarding the putative role of the P2X₇ receptor in triggering purinergic vasotoxicity in the retina and thereby contributing to the progression of diabetic retinopathy.