Neuroprotective effects of angiotensin II type 1 receptor blocker in a rat model of chronic glaucoma

Hongwei Yang, Kazuyuki Hirooka, Kouki Fukuda, Fumio Shiraga

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Purpose. To investigate the neuroprotective effect of candesar-tan, an angiotensin II type 1 receptor (AT1-R) blocker, against the neurotoxicity of the retinal ganglion cells (RGCs) in an animal model of glaucoma. Methods. Cauterization of three episcleral vessels in rats was used to create chronically elevated intraocular pressure (IOP) in one eye. Rats were then treated orally with candesartan (1 mg/kg/d). At 10 weeks, immunohistochemistry was used for quantification of RGC survival and examination of retinal localization of AT1-R. Results. Compared with the contralateral control eyes, there was a consistently elevated IOP of approximately 2.5-fold during the experimental period. At the end of the 10-week candesartan treatment, there were no changes noted for the blood pressure. Compared with the contralateral control eyes that had normal IOP, the RGC survival rate in the central retina of eyes with the chronic, elevated IOP was 46.5% ± 194% (mean ± SD) in the untreated animals and 84.2% ± 4.9% in the candesartan-treated animals (P <0.05; unpaired t -test). In the retina of the normal IOP rat eyes, retinal vessels were positive for AT1-R. After 10 weeks of IOP elevation, immunohistochem-ical analysis of the retina indicated there were many AT1-R-positive RGCs in the candesartan-treated rat, whereas there was an apparent AT1-R decrease in the vehicle-treated rats. Conclusions. In the rat chronic glaucoma model, continuous pharmacologic treatment using candesartan results in significant neuroprotection against RGC loss.

Original languageEnglish
Pages (from-to)5800-5804
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number12
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

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Angiotensin II Type 1 Receptor Blockers
Neuroprotective Agents
Intraocular Pressure
Retinal Ganglion Cells
Glaucoma
Retina
Angiotensin Type 1 Receptor
Cell Survival
Cautery
Retinal Vessels
Animal Models
Immunohistochemistry
candesartan
Blood Pressure
Therapeutics

ASJC Scopus subject areas

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

Cite this

Neuroprotective effects of angiotensin II type 1 receptor blocker in a rat model of chronic glaucoma. / Yang, Hongwei; Hirooka, Kazuyuki; Fukuda, Kouki; Shiraga, Fumio.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 12, 12.2009, p. 5800-5804.

Research output: Contribution to journalArticle

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abstract = "Purpose. To investigate the neuroprotective effect of candesar-tan, an angiotensin II type 1 receptor (AT1-R) blocker, against the neurotoxicity of the retinal ganglion cells (RGCs) in an animal model of glaucoma. Methods. Cauterization of three episcleral vessels in rats was used to create chronically elevated intraocular pressure (IOP) in one eye. Rats were then treated orally with candesartan (1 mg/kg/d). At 10 weeks, immunohistochemistry was used for quantification of RGC survival and examination of retinal localization of AT1-R. Results. Compared with the contralateral control eyes, there was a consistently elevated IOP of approximately 2.5-fold during the experimental period. At the end of the 10-week candesartan treatment, there were no changes noted for the blood pressure. Compared with the contralateral control eyes that had normal IOP, the RGC survival rate in the central retina of eyes with the chronic, elevated IOP was 46.5{\%} ± 194{\%} (mean ± SD) in the untreated animals and 84.2{\%} ± 4.9{\%} in the candesartan-treated animals (P <0.05; unpaired t -test). In the retina of the normal IOP rat eyes, retinal vessels were positive for AT1-R. After 10 weeks of IOP elevation, immunohistochem-ical analysis of the retina indicated there were many AT1-R-positive RGCs in the candesartan-treated rat, whereas there was an apparent AT1-R decrease in the vehicle-treated rats. Conclusions. In the rat chronic glaucoma model, continuous pharmacologic treatment using candesartan results in significant neuroprotection against RGC loss.",
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