Preservation of retinal morphology and functions in royal college surgeons rat by nilvadipine, a Ca(2+) antagonist.
OBJECTIVE
The Royal College of Surgeons (RCS) rat is the most extensively studied animal model for understanding the molecular pathology in inherited retinal degeneration, such as retinitis pigmentosa (RP). The purpose of the present study was to evaluate the pharmacologic effects of several Ca(2+) antagonists on the retinal degeneration of RCS rats.


METHODS
Several Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine, and nifedipine, were intraperitoneally administered and retinal morphology and functions analyzed.


RESULTS
Among the Ca(2+) antagonists, only intraperitoneally administered nilvadipine preserved retinal morphology and electroretinogram responses in RCS rats during the initial stage of retinal degeneration. Studies using immunohistochemistry, RT-PCR, and Western blot analysis revealed significant enhancement of rhodopsin kinase and alphaA-crystallin expression and suppression of caspase 1 and 2 expression in the retina of nilvadipine-treated rats.


CONCLUSIONS
These data suggest that nilvadipine is beneficial for the preservation of photoreceptor cells in RCS rats and can be used to treat some patients with RP.
Yamazaki
Hitoshi
H
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan.
Ohguro
Hiroshi
H
Maeda
Tadao
T
Maruyama
Ikuyo
I
Takano
Yoshiko
Y
Metoki
Tomomi
T
Nakazawa
Mitsuru
M
Sawada
Hajime
H
Dezawa
Mari
M
D000818:Animals; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D053143:Caspase 2; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D003459:Crystallins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D004596:Electroretinography; D005136:Eye Proteins; D019084:Fluorescent Antibody Technique, Indirect; D051606:G-Protein-Coupled Receptor Kinase 1; D007274:Injections, Intraperitoneal; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D012174:Retinitis Pigmentosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002121:Calcium Channel Blockers; D003459:Crystallins; D017931:DNA Primers; D005136:Eye Proteins; D012333:RNA, Messenger; C035100:nilvadipine; D011494:Protein Kinases; D051606:G-Protein-Coupled Receptor Kinase 1; C496765:Grk1 protein, rat; D053143:Caspase 2; D020169:Caspases; D020170:Caspase 1; D009543:Nifedipine