The effect of calcium channel blocker diltiazem on photoreceptor degeneration in the rhodopsin Pro213His rat.
OBJECTIVE
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.
Bush
R A
RA
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor 48105, USA. rbush@umich.edu
Kononen
L
L
Machida
S
S
Sieving
P A
PA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004596:Electroretinography; D005260:Female; D006639:Histidine; D007274:Injections, Intraperitoneal; D008297:Male; D017354:Point Mutation; D011392:Proline; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D012243:Rhodopsin / Q000235:genetics*; D012374:Rod Cell Outer Segment / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D002121:Calcium Channel Blockers; D006639:Histidine; D012243:Rhodopsin; D011392:Proline; D004110:Diltiazem