title: Effect of pitavastatin on experimental choroidal neovascularization in rats.
abstract: The association between the use of statins and age-related macular degeneration (AMD), a leading cause of blindness, has been evaluated in many clinical studies; however, the results have been contradictory. We evaluated the effect of pitavastatin administration on laser-induced experimental choroidal neovascularization (CNV) in rats. Brown Norway rats received pitavastatin (1.0mg/kg per day) for 1day prior to laser-induced CNV and continued to receive the drug for 14days. Fluorescein angiograms were graded by masked observers. CNV area and thickness were assessed by fluorescein isothiocyanate-labeled dextran angiography and histology, respectively. Vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA levels were measured using reverse-transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. Pitavastatin-treated rats had significantly less fluorescence leakage compared with the vehicle-treated rats estimated by CNV score using fluorescein angiography. Both the area and the thickness of CNV in pitavastatin-treated rats were significantly reduced compared with the vehicle-treated rats. Gene expression of VEGF, Ccl-2, and ICAM-1 were significantly decreased by pitavastatin administration in experimental CNV. Thus, we demonstrated that the therapeutic dose of pitavastatin for human hypocholesterolemia effectively suppressed experimental CNV in rats. The use of pitavastatin may be helpful in preventing CNV development in AMD patients.
authors.affiliation: Department of Ophthalmology and Visual Science, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Nina
authors.initials: N
authors.lastname: Sagara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kawaji
authors.forename: Akiomi
authors.initials: A
authors.lastname: Takano
authors.forename: Yasuya
authors.initials: Y
authors.lastname: Inomata
authors.forename: Masaru
authors.initials: M
authors.lastname: Inatani
authors.forename: Mikiko
authors.initials: M
authors.lastname: Fukushima
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005451:Fluorescein Angiography; D005786:Gene Expression Regulation / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D011804:Quinolines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; C108475:pitavastatin