The effect of calcium channel blocker diltiazem on photoreceptor degeneration in the rhodopsin Pro23His rat

R. A. Bush, L. Kononen, S. Machida, P. A. Sieving

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

PURPOSE. To determine whether the calcium chapel blocker D-is-diltiazem promotes photoreceptor survival in rats with the Pro23His rhodopsin mutation. METHODS. Heterozygous Pro23His rhodopsin line 1 rats (n = 11) were treated daily, according to a protocol applied successfully in rd mice, with D-cis-diltiazem hydrochloride increased incrementally from 21 to 54 mg/kg in a divided dose (8 AM and 8 PM) administered by intraperitoneal (IP) injection for 21 days, beginning on days of age 10 through 12. Saline-treated line 1 rats (n = 6) received IP injections of an equal volume of 0.9% saline. Analysis on day 35 of age included dark-adapted corneal electroretinogram (ERG) b- and a-waves recorded from threshold to 0.63 log candela-seconds [cd-s]/m2, saturated a-waves elicited with a 2.1 log cd-s/m2 flash, and morphometry of the outer nuclear layer (ONL) and rod outer segments (ROS). RESULTS. ONL width and cell counts of diltiazem-treated and saline-treated animals at 35 days were reduced to 64%-68% of 15-day-old untreated P23H line 1 retinas. No photoreceptor rescue was found by measuring ONL width (P = 0.84), cell count (P = 0.42), or ROS length (P = 0.85). Functional assays by ERG b-wave threshold (P = 0.57), b-wave maximum amplitude (P = 0.46), and saturated a-wave amplitude (P = 0.59) also showed no rescue. CONCLUSIONS. D-cis-Diltiazem did not rescue photoreceptors of Pro23His rhodopsin mutation line 1 rats treated according to the protocol used in rd mouse.

Original languageEnglish (US)
Pages (from-to)2697-2701
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume41
Issue number9
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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