Absence of photoreceptor rescue with D-cis-diltiazem in the rd mouse

Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1912-5.

Abstract

Purpose: Because of a previous report suggesting that D-cis-diltiazem slows retinal degeneration in rd mice, this study was undertaken to examine the effect of D-cis-diltiazem on photoreceptor structure and function in this line of mice.

Methods: Mice were randomly assigned to daily intraperitoneal injections of D-cis-diltiazem or saline between postnatal days 9 and 24. On postnatal day 26 or 27, retinal function was assessed by recording dark-adapted bright-flash ERGs in all animals. Retinal morphology was examined in fixed sections and in immunolabeled frozen sections. Examiners were masked to the treatment group assignment.

Results: On postnatal days 26 and 27, diltiazem- and saline-treated mice had only one row of remaining photoreceptor cells throughout most of the central retina. Cone cells in the periphery had remnants of inner segments. Total cell counts and separate counts of rod and cone photoreceptor cells by immunostaining were similar in the diltiazem- versus saline-treated mice. Both groups of mice had, on average, comparable subnormal ERG amplitudes.

Conclusions: D-cis-Diltiazem had no detectable effect on preservation of photoreceptor structure and function in rd mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / genetics
  • Animals
  • Calcium Channel Blockers / therapeutic use*
  • Cell Count
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Dark Adaptation
  • Diltiazem / therapeutic use*
  • Electroretinography
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C3H
  • Photic Stimulation
  • Photoreceptor Cells, Vertebrate / drug effects*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / physiology
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / metabolism
  • Retinitis Pigmentosa / physiopathology
  • Rhodopsin / metabolism

Substances

  • Calcium Channel Blockers
  • Rhodopsin
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Pde6b protein, mouse
  • Diltiazem