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R. R. Dubielzig, R. Leedle, T. M. Nork, J. A. VerHoeve, B. J. Christian; Bilateral Optic Atrophy: A Background Finding in Cynomolgus Macaques Used in Toxicologic Research. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5344.
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The incidence, funduscopic findings, electroretinographic (ERG), flash visual evoked potential (VEP), and histopathologic findings of bilateral optic atrophy found in cynomolgus macaques used in regulatory toxicologic research are described.
Cynomologus macaques randomly chosen as a test system for regulatory toxicologic studies had backgound lesions typical of bilateral optic atrophy, a condition previously described only in Rhesus macaques. Fundus photography, ERG, and Flash VEP were performed using standard techniques in some of the animals and histopathology was performed in all animals.
All of the affected animals were 2 to 3 years old and the large majority were of Vietnamese origin. In various studies between 0% and 24% of animals were affected. In one study with 14 affected animals, the histomorphological appearance exhibited a range of severity as follows: severe (6), moderate (3), slight (3) and minimal (2). 4 of the 6 with severe disease and 1 of the 3 with slight disease had optic nerve atrophy recorded on the screening fundus photography; all other animals were considered within the limits of normal variation. Affected animals were not detected by standard ERG or Flash VEP in this study. The morphologic changes consist of a decrease in ganglion cells in the macula and a decrease in axons in the temporal nerve fiber layer and the temporal optic nerve. The condition was always unrelated to the administration of test compounds. No affected animals had any detectable behavioral abnormalities.
Bilateral optic atrophy has been reported in Rhesus macaques originating from China. We report the occurrence of the a similar syndrome in cynomolgus macaques of Vietnamese origin. Given the cynomolgus macque is commonly used in ophthalmic drug safety studies, it is important to characterize the nature of the finding. While the abnormality was not detected by ERG or flash VEP, the majority of markedly affected eyes could be identified by fundus evaluation.
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