Inhibitory effect of orally administered aldose reductase inhibitor SNK-860 on corneal polyol accumulation in galactose-fed rats.
BACKGROUND
Diabetic keratopathy, frequently observed after vitreous surgery, has been thought to be related to the aldose reductase-catalyzed reaction. However, few reports have been published on the chronological changes in polyol accumulation and the effect of the aldose reductase inhibitor in the corneal epithelium or endothelium of galactosemic rats. Consequently, the polyol accumulation in corneal epithelium and endothelium with stroma of 50% galactose-fed rats and the preventive effect of an aldose reductase inhibitor, SNK-860, were biochemically analyzed.


METHODS
Four-week-old male Sprague-Dawley rats were fed a 50% galactose diet without supplement or supplemented with a low (3 mg/kg b.w.) or high (30 mg/kg b.w.) dose of SNK-860 (Sanwa Kagaku Kenkyusho, Japan), or a normal diet. Polyol contents in the corneal epithelium or endothelium with stroma were individually measured using gas-liquid chromatography.


RESULTS
Polyol in corneal epithelia accumulated quickly in the 1st week, reached a maximum at the 3rd week of feeding and then gradually decreased. Low- and high-dose SNK-860 treatment significantly inhibited polyol accumulation in the epithelium and endothelium with stroma, respectively. Changing to the normal or SNK-860 supplemented diets significantly inhibited polyol accumulation.


CONCLUSIONS
This finding indicates that oral administration of a new aldose reductase inhibitor, SNK-860, or systematic treatment of diabetes may be effective in preventing polyol pathway-induced corneal damage by quickly reducing the polyol level.
Kubo
E
E
Department of Ophthalmology, Fukui Medical University, 23-3 Shimoaizuki Matsuoka Yoshida-gun Fukui, 910-1193, Japan,
Nakamura
S
S
Tsuzuki
S
S
Takahashi
Y
Y
Akagi
Y
Y
Mizuno
K
K
Matsubara
A
A
D000284:Administration, Oral; D000449:Aldehyde Reductase / Q000009:adverse effects*; D000818:Animals; D003315:Cornea / Q000201:enzymology*; D003319:Corneal Stroma / Q000187:drug effects / Q000201:enzymology; D004728:Endothelium, Corneal / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004848:Epithelium / Q000201:enzymology; D005690:Galactose / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D011108:Polymers; C024617:polyol; C077139:fidarestat; D000449:Aldehyde Reductase; D005690:Galactose