Format

Send to

Choose Destination
J Pharmacol Toxicol Methods. 2011 Jan-Feb;63(1):102-14. doi: 10.1016/j.vascn.2010.06.008. Epub 2010 Jul 7.

Evaluation of a convenient method of assessing rodent visual function in safety pharmacology studies: effects of sodium iodate on visual acuity and retinal morphology in albino and pigmented rats and mice.

Author information

1
Safety Pharmacology Departmen, Safety Assessment UK, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, United Kingdom. will.redfern@astrazeneca.com

Abstract

INTRODUCTION:

We have evaluated the ability of a semi-automated, optomotor reflex method to assess drug-induced visual dysfunction, in albino and pigmented rats and mice.

METHODS:

Male Han Wistar (HW) and Long Evans (LE) rats and mice (CD-1 and C57BL/6) were tested in a chamber formed by 4 computer monitors displaying a rotating vertical grating, to elicit head-tracking movements. The highest visible grating frequency was taken as the threshold of visual acuity, in cycles per degree (c/d). Animals received an intravenous infusion of either sodium iodate (50mg/kg) or 0.9% w/v NaCl (aq). They were tested 2h later, then re-tested daily for a further 3 days. The time course of the effect was assessed in HW rats over a 6-week period, including electron microscopy, and immunohistochemical analysis of markers of injury and repair in the retina.

RESULTS:

Baseline visual acuities for HW and LE rats were 0.355 ± 0.007 and 0.530 ± 0.004 c/d, respectively, and 0.296 ± 0.003 c/d and 0.370 ± 0.001 c/d for CD-1 and C57BL/6 mice, respectively (n=10 for each). In HW rats there was a dramatic loss of visual acuity 2h after administration of sodium iodate (0.021 ± 0.021 c/d; P<0.001). Less dramatic decreases in visual acuity were seen in LE rats and in the two mouse strains. In HW rats, visual acuity was restored after 4 weeks. This paralleled the histopathological recovery of the peripheral retina, whereas the central retina did not recover.

DISCUSSION:

The method proved to be very convenient, and the stability of visual acuity in vehicle control rats over a 6-week period also demonstrated its suitability for inclusion in long-term toxicity studies. Both albino and pigmented mice and rats are suitable for assessment of retinotoxicity using this method, but albino rats are the most sensitive to sodium iodate.

PMID:
20619348
DOI:
10.1016/j.vascn.2010.06.008
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center