Study of pharmacological effects of nilvadipine on RCS rat retinal degeneration by microarray analysis.
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.
Sato
Motoya
M
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki-shi, Aomori-ken, Japan.
Ohguro
Hiroshi
H
Ohguro
Ikuyo
I
Mamiya
Kazuhisa
K
Takano
Yoshiko
Y
Yamazaki
Hitoshi
H
Metoki
Tomomi
T
Miyagawa
Yasuhiro
Y
Ishikawa
Fotoshi
F
Nakazawa
Mitsuru
M
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
D002121:Calcium Channel Blockers; D012333:RNA, Messenger; C035100:nilvadipine; D016222:Fibroblast Growth Factor 2; D009543:Nifedipine