Polyol metabolism of retrograde axonal transport in diabetic rat large optic nerve fiber.
OBJECTIVE
The role of the polyol pathway metabolism in progressive impairment of retrograde axonal transport was evaluated in the optic nerve of rats with streptozotocin-induced diabetes.


METHODS
Rats with streptozotocin-induced diabetes received a low (3 mg/kg body weight) or high dose (10 mg/kg body weight) of oral aldose reductase inhibitor (ARI). At 1 and 3 months after induction of diabetes, Fluoro-Gold (FG, Chemicon, Temecula, CA) was injected into the dorsal lateral geniculate nucleus. Percentages of FG-labeled large, medium, and small retinal ganglion cells (RGCs) per total population were calculated in the retinas of ARI-treated diabetic, untreated diabetic, and normal control rats.


RESULTS
Mean percentages of FG-labeled large RGCs per total population were significantly decreased in nontreated diabetic rats compared with control animals at 1 month of induced diabetes. This decrease in FG labeling was not observed in both the low- and high-dose ARI-treated diabetic rats. At 3 months of induced diabetes, FG labeling of both large and medium RGCs was significantly decreased. This decrease was completely ameliorated by high-dose ARI treatment.


CONCLUSIONS
These results indicate that diabetes affects retrograde axonal transport progressively through selective impairment of RGCs and that the polyol pathway metabolism is involved in such impairment.
Ino-Ue
M
M
Department of Ophthalmology, Kobe University, School of Medicine. Research Laboratories, Senju Pharmaceutical Co. Ltd., Kobe. Ophthalmic Division, Kobe Children's Hospital, Japan.
Zhang
L
L
Naka
H
H
Kuriyama
H
H
Yamamoto
M
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D052160:Benzothiazoles; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D008297:Male; D008856:Microscopy, Fluorescence; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism*; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013266:Stilbamidines; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D011108:Polymers; D013266:Stilbamidines; D013843:Thiazines; D013844:Thiazoles; C024617:polyol; C088258:SPR 210; D000449:Aldehyde Reductase