Preservation of retinal morphology and functions in royal college surgeons rat by nilvadipine, a Ca(2+) antagonist

Invest Ophthalmol Vis Sci. 2002 Apr;43(4):919-26.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Calcium Channel Blockers / pharmacology*
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Caspase 2
  • Caspases / genetics
  • Caspases / metabolism
  • Crystallins / genetics
  • Crystallins / metabolism
  • DNA Primers / chemistry
  • Disease Models, Animal
  • Electrophoresis, Polyacrylamide Gel
  • Electroretinography
  • Eye Proteins*
  • Fluorescent Antibody Technique, Indirect
  • G-Protein-Coupled Receptor Kinase 1
  • Injections, Intraperitoneal
  • Nifedipine / analogs & derivatives*
  • Nifedipine / pharmacology*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Mutant Strains
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / physiopathology
  • Retina / ultrastructure
  • Retinitis Pigmentosa / metabolism
  • Retinitis Pigmentosa / pathology
  • Retinitis Pigmentosa / physiopathology
  • Retinitis Pigmentosa / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Calcium Channel Blockers
  • Crystallins
  • DNA Primers
  • Eye Proteins
  • RNA, Messenger
  • nilvadipine
  • Protein Kinases
  • G-Protein-Coupled Receptor Kinase 1
  • Grk1 protein, rat
  • Caspase 2
  • Caspases
  • Caspase 1
  • Nifedipine