Effect of the renin inhibitor aliskiren against retinal ischemia-reperfusion injury.
The purpose of this study was to investigate the effect of the renin inhibitor, aliskiren, on retinal ischemia-reperfusion injury. Retinal ischemia was induced by increasing intraocular pressure to 130 mmHg. At 7 days after ischemia, retinal damage was evaluated by measuring the retinal thickness and the number of retinal ganglion cells. Western blot was used to measure changes in the (pro)renin receptor expression. Retinal mRNA expressions of prorenin, angiotensinogen and angiotensin II type 1 receptor (AT1-R) were measured by real-time polymerase chain reaction. Rats were treated with the renin inhibitor, aliskiren. Although the number of retinal ganglion cells and the inner retinal thickness were significantly decreased at 7 days after ischemia, treatment with aliskiren significantly inhibited retinal ischemic injury. Administration of aliskiren increased mRNA expression of prorenin in the retina at 3 h after the reperfusion. The expression of the (pro)renin receptor was not changed after ischemia-reperfusion injury with or without aliskiren. Although there was an increase in the retinal expression of AT1-R at 3 h after the reperfusion, aliskiren administration suppressed this expression. A renin inhibitor attenuated subsequent ischemic damage in the rat retina via the inhibition of the prorenin-induced angiotensin generation.
Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Kaori
K
Tenkumo
Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan. Electronic address: kazuyk@med.kagawa-u.ac.jp.
Kazuyuki
K
Hirooka
Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Shamshad J
SJ
Sherajee
Department of Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Takehiro
T
Nakamura
Department of Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Toshifumi
T
Itano
Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Eri
E
Nitta
Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Tomoyoshi
T
Fujita
Department of Pharmacology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Akira
A
Nishiyama
Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan; Department of Ophthalmology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Fumio
F
Shiraga
D000577:Amides / Q000008:administration & dosage*; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D004195:Disease Models, Animal; D004596:Electroretinography; D005650:Fumarates / Q000008:administration & dosage*; D015918:Infusion Pumps, Implantable; D007429:Intraocular Pressure; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D012084:Renin-Angiotensin System; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012160:Retina / Q000503:physiopathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
D000577:Amides; D000808:Angiotensinogen; D005650:Fumarates; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors; C446481:aliskiren
(pro)renin; aliskiren; angiotensin II type 1 receptor (AT1-R); angiotensinogen; renin; renin-angiotensin-aldosterone-system; retinal ischemia