title: Fasudil, a Rho-associated protein kinase inhibitor, attenuates retinal ischemia and reperfusion injury in rats.
abstract: Abnormal activation of Rho kinase (ROCK) plays a vital role in the pathogenesis of ischemia/reperfusion (I/R)-induced retinal injury. The aim of this study was to investigate whether fasudil, a potent inhibitor of ROCK, has a protective effect on retinal I/R injury in rats and to explore the possible underlying mechanisms. Forty adult Sprague-Dawley rats were randomly assigned into sham, I/R injury model (I/R), model plus normal saline (control), and model plus fasudil (fasudil) groups. Rats in the control and fasudil groups were intravitreously injected with normal saline and fasudil, respectively, 5 min prior to the induction of ischemia. Retinal ischemia was induced by increasing the intraocular pressure to 100 mmHg for 60 min. Overall retinal thickness and retinal cell apoptosis was evaluated by histological analysis and the TUNEL assay, respectively. The protein expression of caspase-3 and the Bax/Bcl-2 mRNA ratio were also examined. Moreover, the retinal expression of inducible nitric oxide synthase (iNOS) was determined by immunohistochemical staining, quantitative real-time RT-PCR and Western blot analysis. Fasudil attenuated the I/R-induced apoptosis of retinal cells in the inner nuclear and ganglion cells of the rat retina. Fasudil significantly decreased the Bax/Bcl-2 mRNA ratio and the expression of caspase-3 and iNOS compared to the control group (P<0.05). Seven days after I/R, the overall retinal thickness in the fasudil group was significantly greater compared to that in the control group (P<0.05). In conclusion, fasudil can protect the rat retina from I/R injury by inhibiting apoptosis and iNOS expression, suggesting that fasudil may have a therapeutic potential for the prevention of retinal diseases associated with I/R.
authors: Department of Ophthalmology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, P.R. China.
authors: Haishan
authors: H
authors: Song
authors: Dianwen
authors: D
authors: Gao
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007511:Ischemia / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000473:pathology*; D012171:Retinal Vessels / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D052247:Nitric Oxide Synthase Type II; D054460:rho-Associated Kinases; D053148:Caspase 3; C049347:fasudil