Abstract
The P2X7 receptor (P2X7R) is a membrane receptor for the extracellular adenosine triphosphate (ATP). It functions as a ligand-gated non-selective cation channel and can mediate formation of a large non-selective membrane pore. Activation of the P2X7R induces multiple downstream events, including oxidative stress, inflammatory responses and cell death. Although the P2X7R has been identified in the retinal pigment epithelium (RPE) and different layers of retina, its biological and pathological functions as well as its downstream signaling pathways in the RPE and retina are not yet fully understood. Better understanding of the function of P2X7R in the RPE and retina under normal and disease states might lead to novel therapeutic targets in retinal diseases, including age-related macular degeneration (AMD). This brief review will mainly focus on recent findings on in vitro and in vivo evidence for the role of the P2X7R in the RPE and AMD.
Highlights
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in developed countries, affecting tens of millions of people worldwide
The vertebrate retina is a structure of ten-layers from closest to farthest from the vitreous body: (1) inner limiting membrane (ILM); (2) nerve fiber layer (NFL); (3) ganglion cell layer (GCL); (4) inner plexiform layer (IPL); (5) inner nuclear layer (INL); (6) outer plexiform layer (OPL); (7) outer nuclear layer (ONL); (8) external limiting membrane (ELM); (9) photoreceptor layer; and (10) the retinal pigment epithelium (RPE) layer
Using primary cultured human RPE cells from different donors, we demonstrated that activation of P2X7 receptor (P2X7R) induces human RPE apoptosis that is dependent on P2X7R-mediated Ca2+
Summary
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in developed countries, affecting tens of millions of people worldwide. It has two forms: dry AMD (geographic atrophy) and wet AMD (neovascular AMD). The dry AMD is the most common form (80%–90%), while wet AMD is less common (10%–20%) and more severe. In wet AMD, excessive amounts of vascular endothelial growth factor (VEGF) were produced by the RPE and other retinal cells. Wet AMD can be managed by anti-VEGF treatment, currently there is neither a cure nor means of prevention for both forms of AMD. This brief review will mainly focus on recent findings on in vitro and in vivo evidence for the role of the P2X7R in the RPE and AMD
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