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.
BACKGROUND
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.


CONCLUSIONS
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.
Redfern
William S
WS
Safety Pharmacology Departmen, Safety Assessment UK, AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, United Kingdom. will.redfern@astrazeneca.com
Storey
Sharon
S
Tse
Karen
K
Hussain
Qasim
Q
Maung
Khine Phu
KP
Valentin
Jean-Pierre
JP
Ahmed
Gulshanara
G
Bigley
Alison
A
Heathcote
Dan
D
McKay
Jennifer S
JS
D000417:Albinism; D000818:Animals; D007452:Iodates / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*; D014792:Visual Acuity / Q000187:drug effects*
D007452:Iodates; C032285:sodium iodate