| First Author | Carver KA | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 482 |
| Issue | 1 | Pages | 81-86 |
| PubMed ID | 27810364 | Mgi Jnum | J:242333 |
| Mgi Id | MGI:5904925 | Doi | 10.1016/j.bbrc.2016.10.140 |
| Citation | Carver KA, et al. (2017) Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD. Biochem Biophys Res Commun 482(1):81-86 |
| abstractText | The P2X7 receptor (P2X7R) is an ATP-gated ion channel that is a key player in oxidative stress under pathological conditions. The P2X7R is expressed in the retinal pigmented epithelium (RPE) and neural retina. Chronic oxidative stress contributes to the pathogenesis of age-related macular degeneration (AMD). Mice lacking Cu, Zn superoxide dismutase (Sod1) developed chronic oxidative stress as well as AMD-like features, but whether the P2X7R plays a causative role in oxidative stress-induced AMD is unknown. Thus, the main purpose of this study was to test if concurrent knockout (KO) of P2X7R could block AMD-like defects seen in Sod1 KO mice. Using multiple approaches, we demonstrate that Sod1 KO causes AMD-like defects, including positive staining for oxidative stress markers, 3-nitrotyrosine and carboxymethyl lysine, thinning of the RPE and retina, thickening of Bruch's membrane, presence of basal laminar and linear deposits, RPE barrier disruption and accumulation of microglia/macrophages. Moreover, we find that Sod1 KO mice accumulate more microparticles (MPs) within RPE/choroid tissues. Concurrent KO of the P2X7R protects against AMD-like defects and MP accumulation in Sod1 KO mice. Together, we show for the first time, that deficiency of P2X7R prevents in vivo oxidative stress-induced accumulation of MPs and AMD-like defects. This work could potentially lead to novel therapies for AMD and other oxidative stress-driven diseases. |
