title: Study of pharmacological effects of nilvadipine on RCS rat retinal degeneration by microarray analysis.
abstract: In our recent study, we found that the Ca(2+) antagonist, nilvadipine caused significant preservation of photoreceptor cells in The Royal College of Surgeons (RCS) rats [Invest. Ophthalmol. Vis. Sci. 43 (2002) 919]. Here, to elucidate the mechanisms of nilvadipine-induced effects we analyzed altered gene expression of 1101 genes commonly expressed in rodent by DNA microarray analysis in the retinas of nilvadipine-treated and untreated RCS rats and SD rat. In the total number of genes, the expression of 30 genes was altered upon administration of nilvadipine to RCS rats, including several genes related to the apoptotic pathway and other mechanisms. Remarkably, neurotrophic factors, FGF-2 and Arc, known to suppress the apoptosis in the central nervous system, were up-regulated. These changes were also confirmed by real-time quantitative (Taqman) RT-PCR and Western blot analysis. Therefore, our present data suggested that administration of nilvadipine to RCS rats increases the expression of endogenous FGF-2 and Arc in retina, and potentially has a protective effect against retinal degeneration.
authors.affiliation: Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki-shi, Aomori-ken, Japan.
authors.forename: Motoya
authors.initials: M
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohguro
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ohguro
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Mamiya
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Tomomi
authors.initials: T
authors.lastname: Metoki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyagawa
authors.forename: Fotoshi
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016923:Cell Death; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D012333:RNA, Messenger; C035100:nilvadipine; D016222:Fibroblast Growth Factor 2; D009543:Nifedipine