Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin ii type 1 receptor

Kouki Fukuda, Kazuyuki Hirooka, Masanori Mizote, Takehiro Nakamura, Toshifumi Itano, Fumio Shiraga

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Purpose. To investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II antagonist against retinal ischemia-reperfusion injury in the rat retina. Methods. Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with an ACE inhibitor (captopril), an angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), an AT2-R antagonist (PD123319), bra-dykinin, or a bradykinin B2 receptor antagonist (icatibant). At 7 days after the ischemia, retinal damage was evaluated. Im-munohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of AT1-R. Dark-adapted full-field electroretinogra-phy (ERG) was also performed. Results. Pretreatment with captopril or candesartan significantly inhibited the ischemic injury of the inner retina. However, PD123319, bradykinin, or icatibant did not reduce the ischemic damage. In control retinas, retinal vessels were positive for AT1-R. In contrast, 12 hours after ischemia, immuno-histochemical analysis detected numerous AT1-R-positive cells in the inner retina in vehicle-treated rats. After ischemia, the production of ROS was detected in retinal cells. However, pretreatment with captopril or candesartan suppressed the production of ROS. On the seventh postoperative day, the amplitudes of the ERG b-waves were significantly lower in the vehicle group than in the groups pretreated with captopril or candesartan. Conclusions. The present findings demonstrate that ischemic damage promotes the expression of AT1-R in the inner retina. Both the ACE inhibitor and the AT1-R antagonist that were examined can block the stimulation of the AT1-R and attenuate the infsequent ischemic damage in the rat retina.

Original languageEnglish
Pages (from-to)3629-3638
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number7
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

Fingerprint

Angiotensin Type 1 Receptor
Reperfusion Injury
Retina
Captopril
Ischemia
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II Type 1 Receptor Blockers
Reactive Oxygen Species
Retinal Vessels
Bradykinin
Intraocular Pressure
Angiotensin II
Neuroprotection
candesartan
Wounds and Injuries

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin ii type 1 receptor. / Fukuda, Kouki; Hirooka, Kazuyuki; Mizote, Masanori; Nakamura, Takehiro; Itano, Toshifumi; Shiraga, Fumio.

In: Investigative Ophthalmology and Visual Science, Vol. 51, No. 7, 07.2010, p. 3629-3638.

Research output: Contribution to journalArticle

Fukuda, Kouki ; Hirooka, Kazuyuki ; Mizote, Masanori ; Nakamura, Takehiro ; Itano, Toshifumi ; Shiraga, Fumio. / Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin ii type 1 receptor. In: Investigative Ophthalmology and Visual Science. 2010 ; Vol. 51, No. 7. pp. 3629-3638.
@article{2b1319328c5848c48fd36635852a1be4,
title = "Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin ii type 1 receptor",
abstract = "Purpose. To investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II antagonist against retinal ischemia-reperfusion injury in the rat retina. Methods. Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with an ACE inhibitor (captopril), an angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), an AT2-R antagonist (PD123319), bra-dykinin, or a bradykinin B2 receptor antagonist (icatibant). At 7 days after the ischemia, retinal damage was evaluated. Im-munohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of AT1-R. Dark-adapted full-field electroretinogra-phy (ERG) was also performed. Results. Pretreatment with captopril or candesartan significantly inhibited the ischemic injury of the inner retina. However, PD123319, bradykinin, or icatibant did not reduce the ischemic damage. In control retinas, retinal vessels were positive for AT1-R. In contrast, 12 hours after ischemia, immuno-histochemical analysis detected numerous AT1-R-positive cells in the inner retina in vehicle-treated rats. After ischemia, the production of ROS was detected in retinal cells. However, pretreatment with captopril or candesartan suppressed the production of ROS. On the seventh postoperative day, the amplitudes of the ERG b-waves were significantly lower in the vehicle group than in the groups pretreated with captopril or candesartan. Conclusions. The present findings demonstrate that ischemic damage promotes the expression of AT1-R in the inner retina. Both the ACE inhibitor and the AT1-R antagonist that were examined can block the stimulation of the AT1-R and attenuate the infsequent ischemic damage in the rat retina.",
author = "Kouki Fukuda and Kazuyuki Hirooka and Masanori Mizote and Takehiro Nakamura and Toshifumi Itano and Fumio Shiraga",
year = "2010",
month = "7",
doi = "10.1167/iovs.09-4107",
language = "English",
volume = "51",
pages = "3629--3638",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "7",

}

TY - JOUR

T1 - Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin ii type 1 receptor

AU - Fukuda, Kouki

AU - Hirooka, Kazuyuki

AU - Mizote, Masanori

AU - Nakamura, Takehiro

AU - Itano, Toshifumi

AU - Shiraga, Fumio

PY - 2010/7

Y1 - 2010/7

N2 - Purpose. To investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II antagonist against retinal ischemia-reperfusion injury in the rat retina. Methods. Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with an ACE inhibitor (captopril), an angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), an AT2-R antagonist (PD123319), bra-dykinin, or a bradykinin B2 receptor antagonist (icatibant). At 7 days after the ischemia, retinal damage was evaluated. Im-munohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of AT1-R. Dark-adapted full-field electroretinogra-phy (ERG) was also performed. Results. Pretreatment with captopril or candesartan significantly inhibited the ischemic injury of the inner retina. However, PD123319, bradykinin, or icatibant did not reduce the ischemic damage. In control retinas, retinal vessels were positive for AT1-R. In contrast, 12 hours after ischemia, immuno-histochemical analysis detected numerous AT1-R-positive cells in the inner retina in vehicle-treated rats. After ischemia, the production of ROS was detected in retinal cells. However, pretreatment with captopril or candesartan suppressed the production of ROS. On the seventh postoperative day, the amplitudes of the ERG b-waves were significantly lower in the vehicle group than in the groups pretreated with captopril or candesartan. Conclusions. The present findings demonstrate that ischemic damage promotes the expression of AT1-R in the inner retina. Both the ACE inhibitor and the AT1-R antagonist that were examined can block the stimulation of the AT1-R and attenuate the infsequent ischemic damage in the rat retina.

AB - Purpose. To investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II antagonist against retinal ischemia-reperfusion injury in the rat retina. Methods. Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with an ACE inhibitor (captopril), an angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), an AT2-R antagonist (PD123319), bra-dykinin, or a bradykinin B2 receptor antagonist (icatibant). At 7 days after the ischemia, retinal damage was evaluated. Im-munohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of AT1-R. Dark-adapted full-field electroretinogra-phy (ERG) was also performed. Results. Pretreatment with captopril or candesartan significantly inhibited the ischemic injury of the inner retina. However, PD123319, bradykinin, or icatibant did not reduce the ischemic damage. In control retinas, retinal vessels were positive for AT1-R. In contrast, 12 hours after ischemia, immuno-histochemical analysis detected numerous AT1-R-positive cells in the inner retina in vehicle-treated rats. After ischemia, the production of ROS was detected in retinal cells. However, pretreatment with captopril or candesartan suppressed the production of ROS. On the seventh postoperative day, the amplitudes of the ERG b-waves were significantly lower in the vehicle group than in the groups pretreated with captopril or candesartan. Conclusions. The present findings demonstrate that ischemic damage promotes the expression of AT1-R in the inner retina. Both the ACE inhibitor and the AT1-R antagonist that were examined can block the stimulation of the AT1-R and attenuate the infsequent ischemic damage in the rat retina.

UR - http://www.scopus.com/inward/record.url?scp=77955884119&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955884119&partnerID=8YFLogxK

U2 - 10.1167/iovs.09-4107

DO - 10.1167/iovs.09-4107

M3 - Article

VL - 51

SP - 3629

EP - 3638

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 7

ER -