Study of drug effects of calcium channel blockers on retinal degeneration of rd mouse.
In the present study, we studied drug effects of Ca(2+) antagonists on the retinal degeneration of rd mouse to evaluate their efficacy. Several kinds of Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine or nifedipine were administrated intraperitoneally and thereafter retinal morphology and functions were analyzed. In addition, we performed DNA microarray analysis both in nilvadipine treated and control retinas to understand their drug effects at molecular levels. We found that nilvadipine caused significant preservation of retinal thickness in rd mouse during the initial stage of the retinal degeneration, and nicardipine showed also significant but lesser preservation than nilvadipine. However, we recognized no preservation effects of diltiazem and nifedipine. In the total 3774 genes, the expressions of 27 genes were altered upon administration of nilvadipine, including several genes related to the apoptotic pathway, neuro-survival factor, Ca(2+) metabolisms, and other mechanisms. It is suggested that some types of Ca(2+) channel blockers, such as nilvadipine and nicardipine, are able to preserve photoreceptor cells in rd mouse and can potentially be used to treat some RP patients.
Takano
Yoshiko
Y
Department of Ophthalmology, Hirosaki University School of Medicine, Japan.
Ohguro
Hiroshi
H
Dezawa
Mari
M
Ishikawa
Hiroto
H
Yamazaki
Hitoshi
H
Ohguro
Ikuyo
I
Mamiya
Kazuhisa
K
Metoki
Tomomi
T
Ishikawa
Futoshi
F
Nakazawa
Mitsuru
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020169:Caspases / Q000235:genetics; D004110:Diltiazem / Q000494:pharmacology; D004596:Electroretinography; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D062805:Synaptogyrins
D002121:Calcium Channel Blockers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D062805:Synaptogyrins; C035100:nilvadipine; D016222:Fibroblast Growth Factor 2; D009529:Nicardipine; D020169:Caspases; D004110:Diltiazem; D009543:Nifedipine