Effects of aldose reductase inhibitor CT-112 on the corneal epithelial barrier of galactose-fed rats.
OBJECTIVE
To investigate whether the barrier function of the corneal epithelium is disrupted in galactosemic rats, and to assess the effects of the aldose reductase inhibitor CT-112, in the form of eyedrops, on the corneal epithelial barrier in galactosemic rats.


METHODS
Forty rats were divided into 3 groups based on their diet: a control group, a galactose group and a CT-112 treated galactose group (CT-112 group). After 3 weeks, 31 rats from the 3 groups were subjected to fluorophotometry, in which fluorescein (F) was instilled into one eye and carboxyfluorescein (CF) was instilled into the other eye in a random fashion. The F and CF uptakes were then measured at the central cornea by a slit-lamp fluorophotometer. Three rats from each group were exposed to a horseradish peroxidase (HRP) solution for one hour, and the HRP-reactive substances within the corneal epithelium were also examined via electron microscopy.


RESULTS
There was significantly higher F uptake in the galactose group than in the control (p = 0.003) and CT-112 groups (p = 0.028). There were no significant differences in CF uptake between the 3 groups. Histologically, HRP-reactive substances were found in much greater quantities within the superficial corneal cells of the galactose group than in the control or CT-112 groups.


CONCLUSIONS
These results suggest that cell membrane disruption, as detected by F uptake and HRP penetration, was found in the superficial corneal cells of galactose-fed rats, and that intercellular junction integrity can be assayed by CF uptake and histological evaluation. Moreover, CT-112 eyedrops were effective in improving the corneal epithelial barrier dysfunction of galactose-fed rats.
Yokoi
N
N
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Japan.
Niiya
A
A
Komuro
A
A
Yokogaki
S
S
Naka
H
H
Awata
T
T
Honma
Y
Y
Yamada
J
J
Tei
M
M
Kinoshita
S
S
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000648:ultrastructure; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D015590:Fluorophotometry; D005690:Galactose / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D004791:Enzyme Inhibitors; D013844:Thiazoles; D045162:Thiazolidinediones; C051003:risarestat; D000449:Aldehyde Reductase; D005690:Galactose