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The Effect of Calcium Channel Blocker Diltiazem on Photoreceptor Degeneration in the Rhodopsin Pro213His Rat

The Effect of Calcium Channel Blocker Diltiazem on Photoreceptor Degeneration in the Rhodopsin Pro213His Rat

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

Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2697-701.

PMID: 10937585

Abstract:

Purpose:
To determine whether the calcium channel blocker D-cis-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 (i.p.) injection for 21 days, beginning on days of age 10 through 12. Saline-treated line 1 rats (n = 6) received i.p. 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP33286225-A	(+)-cis-Diltiazem hydrochloride		33286-22-5	Price

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