| First Author | Notomi S | Year | 2011 |
| Journal | Am J Pathol | Volume | 179 |
| Issue | 6 | Pages | 2798-809 |
| PubMed ID | 21983632 | Mgi Jnum | J:180087 |
| Mgi Id | MGI:5305385 | Doi | 10.1016/j.ajpath.2011.08.035 |
| Citation | Notomi S, et al. (2011) Critical involvement of extracellular ATP acting on P2RX7 purinergic receptors in photoreceptor cell death. Am J Pathol 179(6):2798-809 |
| abstractText | Stressed cells release ATP, which participates in neurodegenerative processes through the specific ligation of P2RX7 purinergic receptors. Here, we demonstrate that extracellular ATP and the more specific P2RX7 agonist, 2'- and 3'-O-(4-benzoylbenzoyl)-ATP, both induce photoreceptor cell death when added to primary retinal cell cultures or when injected into the eyes from wild-type mice, but not into the eyes from P2RX7(-/-) mice. Photoreceptor cell death was accompanied by the activation of caspase-8 and -9, translocation of apoptosis-inducing factor from mitochondria to nuclei, and TUNEL-detectable chromatin fragmentation. All hallmarks of photoreceptor apoptosis were prevented by premedication or co-application of Brilliant Blue G, a selective P2RX7 antagonist that is already approved for the staining of internal limiting membranes during ocular surgery. ATP release is up-regulated by nutrient starvation in primary retinal cell cultures and seems to be an initializing event that triggers primary and/or secondary cell death via the positive feedback loop on P2RX7. Our results encourage the potential application of Brilliant Blue G as a novel neuroprotective agent in retinal diseases or similar neurodegenerative pathologies linked to excessive extracellular ATP. |
