Systemic administration of nilvadipine delays photoreceptor degeneration of heterozygous retinal degeneration slow (rds) mouse.
To investigate the effect of nilvadipine, a calcium channel blocker, upon the retina of retinal degeneration slow (rds) mouse, nilvadipine was intraperitoneally injected into heterozygous rds mice for up to 200 days. The effect of nilvadipine was evaluated by electroretinography (ERG), light and electron microscopies, DNA microarray, quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and western-blot analysis. After nilvadipine treatment, both a- and b-waves of ERG were significantly higher than in the control group (p<0.01). Although there was no difference in histological findings by light microscopy between the nilvadipine treated group and control group, apparent preservation of photoreceptor disc was demonstrated by electron microscopy in the treated group. Rhodopsin level was also increased in the treated group comparing to the control group. The DNA microarray analysis detected increased expression of genes encoding proteins which function in protein synthesis, growth factors and neurotrophic factor like ciliary neurotrophic factor (CNTF) and fibroblast growth factors (FGFs22 and 13). Decreased expression of genes coding for proteins related to proteolysis, apoptosis and growth factor (FGF18) was also demonstrated. Increased expression of CNTF, FGF22 and FGF13 and decreased expression of FGF18 were confirmed by both quantitative RT-PCR and western-blot analysis. In addition, FGF2 was constitutively expressed in both treated and control groups. Since CNTF has been known to retard retinal degeneration by rds mouse or other models of inherited retinal degeneration, it is possible that nilvadipine has a photoreceptor survival effect on rds retinal degeneration partly by enhancing expression of endogenous CNTF in the retina.
Takeuchi
Kimio
K
Department of Ophthalmology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Nakazawa
Mitsuru
M
Mizukoshi
Sayuri
S
D000818:Animals; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004596:Electroretinography / Q000187:drug effects; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D002121:Calcium Channel Blockers; D005136:Eye Proteins; C035100:nilvadipine; D009543:Nifedipine