The effect of pantethine and ultraviolet-B radiation on the development of lenticular opacity in the emory mouse.
OBJECTIVE
Few studies have examined the impact of long-term treatments or exposures on the development of cataract in maturity-onset animal models. We studied the effect of treatment with D-pantethine and exposure to ultraviolet-B (UVB) radiation on the development of lenticular opacity in the Emory mouse.


METHODS
A total of 164 Emory mice were randomized by litter at weaning to exposure to UVB light at 12 mJ/cm(2) for 6 hr/day (UV) or usual room light (A), and within litter, were further randomized to bi-weekly intra-peritoneal injections of 0.8 g/kg pantethine (T) or no treatment (C). Retro illumination lens photos were taken at 2, 4, 6, 8, and 10 months after weaning, and graded in masked fashion. The animals were sacrificed at 10 months and the lenses analyzed for total pantethine and total cysteamine.


RESULTS
Lens pantethine and cysteamine levels were significantly (P < 0.001) higher for the T as compared to C litters. Mean cataract grade increased monotonically over time for all four groups. Unadjusted mean grade for the AT group at 8 (1.32) and 10 (1.86) months appeared lower than for the other groups (AC: 2.17, 2.39; UVC: 1.77, 2.40; UVT: 1.88, 2.37). However, the mean grade for the pantethine-treated litters did not differ significantly from the untreated litters except at 2 months (when untreated litters had significantly lower grades), when adjusting for UV treatment, gender and litter effect. No significant difference in cataract score existed between UV-exposed and ambient litters. Mortality was higher among pantethine-treated (hazard ratio = 1.8, p = 0.05) and UV-exposed animals (hazard ratio = 1.8, p = 0. 03) than among the untreated and unexposed litters.


CONCLUSIONS
Significantly increased lens levels of pantethine are achieved with long-term intra-peritoneal dosing. The impact of pantethine on the progression of lenticular opacity in the Emory mouse is less than has been reported in other models. This level of chronic UVB exposure appeared to have no effect on the development of cataract in this model.
Congdon
N T
NT
Johns Hopkins University, Dana Center for Preventive Ophthalmology, Baltimore, MD 21205, USA. ncongdon@jhmi.edu
West
S T
ST
Duncan
D T
DT
Fisher
D T
DT
Vitale
S T
ST
Rieger
K T
KT
Urist
J T
JT
Hazelwood
D T
DT
Sanchez
A T
AT
Pham
T
T
Cole
L
L
McNaughton
C
C
D000818:Animals; D002386:Cataract / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003543:Cysteamine / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D010204:Pantetheine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014466:Ultraviolet Rays
D010204:Pantetheine; D003543:Cysteamine; C005425:pantethine