The research efforts in this proposal are aimed at purifying and characterizing human lens aldose reductase, polyol dehydrogenase and aldehyde dehydrogenase type enzymes (glyceraldehyde-3-P dehydrogenase, aldehyde dehydrogenase, and formaldehyde dehydrogenase). Aldose reductase and polyol dehydrogenase comprise the sorbitol pathway. Their combined activities lead to the accumulation of sorbitol and fructose in the lens and appear to initiate the diabetic process in diabetic animals. Despite the potential and pivotal role that these enzymes may play in causing diabetic cataract in the human lens, virtually nothing is known at present about the properties and hence, regulating features of these enzymes in the human lens. We propose to purify and characterize these enzymes from the human lens and thus determine a means for modifying their activity and hence, possibly preventing human diabetic cataract formation. During the course of examining the sorbitol pathway in the human lens, we became aware that other enzymes are present that affect aldehyde metabolism. The human lens contains an aldehyde dehydrogenase system that converts aldehydes to their carboxylic acid forms. This alternate system may compete with aldose reductase for glyceraldehyde as substrate. Furthermore, the aldehyde dehydrogenase system provides a mechanism to the lens for rendering a variety of aldehydes that cross-link lens proteins, i.e., cause aggregation, non-reactive. Methods of purification as well as certain criteria for characterizing and identifying the precise aldehyde dehydrogenase(s) that """"""""detoxify"""""""" cross-linking reactive aldehydes in the lens are described.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003565-05
Application #
3257918
Study Section
(SSS)
Project Start
1980-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1986-11-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code