A Na+/Ca2+ exchanger isoform, NCX1, is involved in retinal cell death after N-methyl-D-aspartate injection and ischemia–reperfusion
✍ Scribed by Y. Inokuchi; M. Shimazawa; Y. Nakajima; I. Komuro; T. Matsuda; A. Baba; M. Araie; S. Kita; T. Iwamoto; H. Hara
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 639 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
We investigated the expression of Na^+^/Ca^2+^ exchanger (NCX) and the functional role of NCX in retinal damage by using NCX1‐heterozygous deficient mice (NCX1^+/−^) and SEA0400 (2‐[4‐[(2,5‐difluorophenyl)methoxy] phenoxy]‐5‐ethoxyaniline), a selective NCX inhibitor in vivo. We also examined the role of NCX in oxygen–glucose deprivation (OGD) stress with a retinal ganglion cell line (RGC‐5) cell culture in vitro. The expression of NCX1 was confirmed and entirely localized in retina by immunoblotting and immunohistochemistry, respectively. NCX1^+/−^ mice possessed significant protection against retinal damage induced by intravitreal injection of N‐methyl‐D‐aspartate (NMDA). SEA0400 at 3 and 10 mg/kg significantly reduced NMDA‐ or high intraocular pressure–induced retinal cell damage in mice. Furthermore, SEA0400 reduced the number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick‐end labeling)‐positive cells and the expression of phosphorylated mitogen‐activated protein kinases (ERK1/2, JNK, p38) induced by NMDA injection. In RGC‐5, SEA0400 at 0.3 and 1 μM significantly inhibited OGD‐induced cell damage. OGD‐induced cell damage was aggravated by ouabain (a Na^+^,K^+^‐ATPase inhibitor) at 100 μM, and this increased damage was significantly reduced by SEA0400 at 1 μM. In conclusion, these results suggest that NCX1 may play a role in retinal cell death induced by NMDA and ischemia–reperfusion. © 2008 Wiley‐Liss, Inc.