Galactose-induced cataract formation in guinea pigs: morphologic changes and accumulation of galactitol.
OBJECTIVE
To develop and characterize a new model of galactose-induced cataract formation in young, 3- to 4-week-old Hartley guinea pigs.


METHODS
Experimental animals were fed 50% galactose in powdered guinea pig chow containing 0.5 g ascorbate/kg diet. Control animals were fed normal powdered guinea pig chow (0.5 g ascorbate/kg diet). Lenses from all animals were subjected to photo-slit-lamp examination, light microscopic analysis, and high-pressure liquid chromatography (HPLC) analysis of polyol content.


RESULTS
Photo-slit-lamp examination indicated initial opacities in equatorial subcapsular region between 3 and 5 days in all galactose-fed animals (20/20); opacities progressed toward the anterior pole when diet was extended to 14 days. Histologic analysis of the equatorial changes confirmed progressive cataract formation consisting of small intra-fibrillar vacuoles in the pre-equatorial region (3 days), an increased number of enlarged and coalesced vacuoles (6 days), and progressive tissue swellings with cellular disruption and signs of epithelial multilayering (14 days). The anterior epithelium showed increased cell height and swelling after 3 days of the galactose diet. HPLC analysis of lens tissue indicated progressive accumulation of galactitol, 18 mM after 3 days, which plateaued to about 30 mM between 6 and 14 days. The level of myo-inositol dropped from a control value of 2.8 +/- 0.7 mM to 1.5 +/- 0.7 mM after 3 days, and was nearly undetectable after 14 days of the galactose diet.


CONCLUSIONS
The current study suggests that the guinea pig model may serve as a valuable new tool to study sugar-induced cataract formation and to characterize the early morphologic and biochemical events in cataractogenesis.
Mackic
J B
JB
Department of Neurological Surgery, Children's Hospital of Los Angeles, University of Southern California School of Medicine 90033.
Ross-Cisneros
F N
FN
McComb
J G
JG
Bekhor
I
I
Weiss
M H
MH
Kannan
R
R
Zlokovic
B V
BV
D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005260:Female; D004376:Galactitol / Q000378:metabolism*; D005690:Galactose; D006168:Guinea Pigs; D007294:Inositol / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats
D004376:Galactitol; D007294:Inositol; D005690:Galactose