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Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD.

Publication ,  Journal Article
Carver, KA; Lin, CM; Bowes Rickman, C; Yang, D
Published in: Biochem Biophys Res Commun
January 1, 2017

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.

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Published In

Biochem Biophys Res Commun

DOI

EISSN

1090-2104

Publication Date

January 1, 2017

Volume

482

Issue

1

Start / End Page

81 / 86

Location

United States

Related Subject Headings

  • Superoxide Dismutase-1
  • Stress, Physiological
  • Receptors, Purinergic P2X7
  • Oxygen
  • Oxidative Stress
  • Mice, Knockout
  • Mice
  • Male
  • Macular Degeneration
  • Female
 

Citation

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Carver, K. A., Lin, C. M., Bowes Rickman, C., & Yang, D. (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. https://doi.org/10.1016/j.bbrc.2016.10.140
Carver, Kyle A., C. M. Lin, Catherine Bowes Rickman, and Dongli Yang. “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, no. 1 (January 1, 2017): 81–86. https://doi.org/10.1016/j.bbrc.2016.10.140.
Carver, Kyle A., et al. “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, vol. 482, no. 1, Jan. 2017, pp. 81–86. Pubmed, doi:10.1016/j.bbrc.2016.10.140.
Carver KA, Lin CM, Bowes Rickman C, Yang D. 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. 2017 Jan 1;482(1):81–86.
Journal cover image

Published In

Biochem Biophys Res Commun

DOI

EISSN

1090-2104

Publication Date

January 1, 2017

Volume

482

Issue

1

Start / End Page

81 / 86

Location

United States

Related Subject Headings

  • Superoxide Dismutase-1
  • Stress, Physiological
  • Receptors, Purinergic P2X7
  • Oxygen
  • Oxidative Stress
  • Mice, Knockout
  • Mice
  • Male
  • Macular Degeneration
  • Female