Purpose. D-Galactose is widely utilized in studies on sugar cataract formation. Kinetic studies with purified dog lens aldose reductase (AR) indicate that 3-fluoro-3-deoxygalactose (3-FDGal) is a better sugar substrate than galactose. To gain new insights into the role of polyol accumulation in sugar cataract formation the localized metabolism of 3-FDGal has been investigated by 19F-NMR spectroscopy and magnetic resonance imaging (MRI). Methods. The metabolism of 3-FDGal was monitored in whole dog lens and dog lens epithelial cells incubated in vitro in medium containing 3-FDGal. Polyol distribution was visualized by MRI. Results. Both whole dog lens and epithelial cells cultured in medium containing 3-FDGal rapidly accumulated 3-fluoro-3-deoxygalactitol and this accumulation was inhibited by co-incubation with 10 μM of the AR inhibitor AL-1576. In the intact lens small vacuoles developed in the equatorial region similar to those observed in vivo in galactose-fed dogs. Vacuolar degeneration was also observed in epithelial cells cultured in medium containing 3-FDGal. Both phenomena were prevented by coincubation with the AR inhibitor AL-1576. Imaging of 3-fluoro-3-deoxysorbitol indicated that polyol accumulation was localized predominantly in the anterior cortex and equatorial bow regions. This corresponds to the immunohistochemically observed localization of aldose reductase. Conclusions. Use of 3-FDGal as a substrate to investigate sugar cataract formation in dog lens indicates that polyol formation is predominantly localized in the anterior cortex and bow region. Localized accumulation of polyol may produce localized osmotic stress.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience