Angiotensin II type 1 receptor blockade suppresses light-induced neural damage in the mouse retina

Toshio Narimatsu, Yoko Ozawa, Seiji Miyake, Norihiro Nagai, Kazuo Tsubota

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Exposure to light contributes to the development and progression of retinal degenerative diseases. However, the mechanisms underlying light-induced tissue damage are not fully understood. Here, we examined the role of angiotensin II type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system, in light-induced retinal damage. Light-exposed Balb/c mice that were treated with the AT1R blockers (angiotensin II receptor blockers; ARBs) valsartan, losartan, and candesartan before and after the light exposure exhibited attenuated visual function impairment, compared to vehicle-treated mice. This effect was dose-dependent and observed across the ARB class of inhibitors. Further evaluation of valsartan showed that it suppressed a number of light-induced retinal effects, including thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment, and increased levels of reactive oxygen species (ROS). The role of ROS in retinal pathogenesis was investigated further using the antioxidant N-acetyl-l-cysteine (NAC). Treatment of light-exposed mice with NAC before the light exposure suppressed the visual function impairment and photoreceptor cell histological changes due to apoptosis. Moreover, treatment with valsartan or NAC suppressed the induction of c-fos (a component of the AP-1 transcription factor) and the upregulation of fasl (a proapoptotic molecule whose transcript is regulated downstream of AP-1). Our results suggest that AT1R signaling mediates light-induced apoptosis, by increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R blockade may represent a new therapeutic approach for preventing light-induced retinal neural tissue damage.

Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalFree Radical Biology and Medicine
Volume71
DOIs
Publication statusPublished - 2014

Fingerprint

Angiotensin Type 1 Receptor
Retina
Valsartan
Light
Acetylcysteine
Photoreceptor Cells
Cysteine
Reactive Oxygen Species
Vision Disorders
Transcription Factor AP-1
Apoptosis
Tissue
Angiotensin II Type 1 Receptor Blockers
Retinal Diseases
Molecules
Losartan
Angiotensin Receptor Antagonists
Angiotensins
Renin-Angiotensin System
Renin

Keywords

  • Angiotensin II type 1 receptor
  • Apoptosis
  • Light
  • Oxidative stress
  • Retina

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Medicine(all)

Cite this

Angiotensin II type 1 receptor blockade suppresses light-induced neural damage in the mouse retina. / Narimatsu, Toshio; Ozawa, Yoko; Miyake, Seiji; Nagai, Norihiro; Tsubota, Kazuo.

In: Free Radical Biology and Medicine, Vol. 71, 2014, p. 176-185.

Research output: Contribution to journalArticle

@article{97d9729054ad4fdd9d8b981f05b6693f,
title = "Angiotensin II type 1 receptor blockade suppresses light-induced neural damage in the mouse retina",
abstract = "Exposure to light contributes to the development and progression of retinal degenerative diseases. However, the mechanisms underlying light-induced tissue damage are not fully understood. Here, we examined the role of angiotensin II type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system, in light-induced retinal damage. Light-exposed Balb/c mice that were treated with the AT1R blockers (angiotensin II receptor blockers; ARBs) valsartan, losartan, and candesartan before and after the light exposure exhibited attenuated visual function impairment, compared to vehicle-treated mice. This effect was dose-dependent and observed across the ARB class of inhibitors. Further evaluation of valsartan showed that it suppressed a number of light-induced retinal effects, including thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment, and increased levels of reactive oxygen species (ROS). The role of ROS in retinal pathogenesis was investigated further using the antioxidant N-acetyl-l-cysteine (NAC). Treatment of light-exposed mice with NAC before the light exposure suppressed the visual function impairment and photoreceptor cell histological changes due to apoptosis. Moreover, treatment with valsartan or NAC suppressed the induction of c-fos (a component of the AP-1 transcription factor) and the upregulation of fasl (a proapoptotic molecule whose transcript is regulated downstream of AP-1). Our results suggest that AT1R signaling mediates light-induced apoptosis, by increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R blockade may represent a new therapeutic approach for preventing light-induced retinal neural tissue damage.",
keywords = "Angiotensin II type 1 receptor, Apoptosis, Light, Oxidative stress, Retina",
author = "Toshio Narimatsu and Yoko Ozawa and Seiji Miyake and Norihiro Nagai and Kazuo Tsubota",
year = "2014",
doi = "10.1016/j.freeradbiomed.2014.03.020",
language = "English",
volume = "71",
pages = "176--185",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Angiotensin II type 1 receptor blockade suppresses light-induced neural damage in the mouse retina

AU - Narimatsu, Toshio

AU - Ozawa, Yoko

AU - Miyake, Seiji

AU - Nagai, Norihiro

AU - Tsubota, Kazuo

PY - 2014

Y1 - 2014

N2 - Exposure to light contributes to the development and progression of retinal degenerative diseases. However, the mechanisms underlying light-induced tissue damage are not fully understood. Here, we examined the role of angiotensin II type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system, in light-induced retinal damage. Light-exposed Balb/c mice that were treated with the AT1R blockers (angiotensin II receptor blockers; ARBs) valsartan, losartan, and candesartan before and after the light exposure exhibited attenuated visual function impairment, compared to vehicle-treated mice. This effect was dose-dependent and observed across the ARB class of inhibitors. Further evaluation of valsartan showed that it suppressed a number of light-induced retinal effects, including thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment, and increased levels of reactive oxygen species (ROS). The role of ROS in retinal pathogenesis was investigated further using the antioxidant N-acetyl-l-cysteine (NAC). Treatment of light-exposed mice with NAC before the light exposure suppressed the visual function impairment and photoreceptor cell histological changes due to apoptosis. Moreover, treatment with valsartan or NAC suppressed the induction of c-fos (a component of the AP-1 transcription factor) and the upregulation of fasl (a proapoptotic molecule whose transcript is regulated downstream of AP-1). Our results suggest that AT1R signaling mediates light-induced apoptosis, by increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R blockade may represent a new therapeutic approach for preventing light-induced retinal neural tissue damage.

AB - Exposure to light contributes to the development and progression of retinal degenerative diseases. However, the mechanisms underlying light-induced tissue damage are not fully understood. Here, we examined the role of angiotensin II type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system, in light-induced retinal damage. Light-exposed Balb/c mice that were treated with the AT1R blockers (angiotensin II receptor blockers; ARBs) valsartan, losartan, and candesartan before and after the light exposure exhibited attenuated visual function impairment, compared to vehicle-treated mice. This effect was dose-dependent and observed across the ARB class of inhibitors. Further evaluation of valsartan showed that it suppressed a number of light-induced retinal effects, including thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment, and increased levels of reactive oxygen species (ROS). The role of ROS in retinal pathogenesis was investigated further using the antioxidant N-acetyl-l-cysteine (NAC). Treatment of light-exposed mice with NAC before the light exposure suppressed the visual function impairment and photoreceptor cell histological changes due to apoptosis. Moreover, treatment with valsartan or NAC suppressed the induction of c-fos (a component of the AP-1 transcription factor) and the upregulation of fasl (a proapoptotic molecule whose transcript is regulated downstream of AP-1). Our results suggest that AT1R signaling mediates light-induced apoptosis, by increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R blockade may represent a new therapeutic approach for preventing light-induced retinal neural tissue damage.

KW - Angiotensin II type 1 receptor

KW - Apoptosis

KW - Light

KW - Oxidative stress

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=84921405980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921405980&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2014.03.020

DO - 10.1016/j.freeradbiomed.2014.03.020

M3 - Article

C2 - 24662196

AN - SCOPUS:84921405980

VL - 71

SP - 176

EP - 185

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -