[Electrophysiological and histopathological study on visual toxicity of clioquinol].
OBJECTIVE
To evaluate the effect of clioquinol on the optic nerve and retina of rhesus monkeys by ophthalmoscopy, electrophysiology and histopathology.


METHODS
Clioquinol was given orally to 5 monkeys, gradually increasingly from 100 mg/kg/day up to 14 months(total dosage 227 g/kg). Ophthalmoscopy, erectroretinogram(ERG), visual evoked potential(VEP) and histopathological examination of enucleated eyeballs were done periodically up to 10 years.


RESULTS
The margin of the optic disc was not clear at the early stage, but the colour became atrophic at the late stage. VEP maximum amplitude decreased quickly at the early stage and the amplitude of ERG a and b waves and oscillatory potential decreased gradually. 37 months after the discontinuation of administration of VEP, ERG amplitude increased gradually. Swelling of axons and disorganization of the myelin sheath were noticed 2.5 months after beginning treatment. Swelling of the peripapillary nerve fiber layer was seen 5.5 months after beginning treatment. Karyorrhexis was seen in the inner layer of the retina after 12.5 months. Axonal swelling disappeared and the myelin sheath became reorganized 9 months after the discontinuation of treatment.


CONCLUSIONS
Clioquinol produced an early decrease of electrophysiological function, but recovery of function was seen after discontinuation of treatment. The degeneration of axons and myelin sheath continued during treatment, and interruption of the degeneration was seen after discontinuation of treatment.
Yamada
Shuzo
S
Department of Ophthalmology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan.
Okisaka
Shigekuni
S
Yoshii
Masaru
M
Mizukawa
Atsushi
A
Yanashima
Kenji
K
D000818:Animals; D007464:Clioquinol / Q000633:toxicity*; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D005260:Female; D008253:Macaca mulatta; D009887:Ophthalmoscopy; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology; D012160:Retina / Q000187:drug effects* / Q000473:pathology
D007464:Clioquinol