We have studied the regulatory actions of aldose reductase inhibition during the ONSET and REVERSAL of sugar cataractogenesis over the past 5 years; the reversal studies are still in progress. We will CONTINUE to address the 4 questions previously asked using the aldose reductase inhibitor, sorbinil, 2 in vivo cataract systems (galactose and streptozotocin) and methodology including scanning electron microscopy and gas liquid chromatography. In the reversal studies, we found that a direct correlation existed between lens myo-inositol content, cell integrity and lens transparency. Thus, a NEW OBJECTIVE is to further determine the INTERRELATIONSHIP BETWEEN MYO-INOSITOL AND THE POLYOL PATHWAY. Furthermore we will expand our study to include: 1.) a slowly progressing, genetically determined diabetic cataract model, BB RAT, 2.) a new therapeutic agent, myo-inositol and determination of its interrelationship with sorbinil to ascertain whether a synergistic effect occurs to promote the restoration of lens transparency, 3.) to analyze lens phosphatidylinositol content because myo-inositol serves as a precursor, 4.) to perform hexose transport studies to further analyze the role of sorbinil on uptake and efflux of myo-inositol, glucose and lens cation content. Thus, we will test the hypothesis that hyperglycemic concentrations of glucose competitively inhibit myo-inositol uptake, which in turn via phosphatidylinositol may lead to significant changes in cell homeostasis. The possibility of modifying the extent and rate of the reparative process by manipulation of myo-inositol and aldose reductase inhibition will be explored. Our long term objective is to enhance lens integrity in patients who exhibit various stages of diabetic cataract.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY003226-07
Application #
3257511
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1980-07-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107
Diecke, F P; Beyer-Mears, A (1997) A mechanism for regulatory volume decrease in cultured lens epithelial cells. Curr Eye Res 16:279-88
Beyer-Mears, A; Diecke, F P; Mistry, K et al. (1997) Effect of pyruvate on lens myo-inositol transport and polyol formation in diabetic cataract. Pharmacology 55:78-86
Beyer-Mears, A; Diecke, F P; Mistry, K et al. (1997) Comparison of the effects of Zopolrestat and Sorbinil on lens myo-inositol influx. Pharmacology 54:76-83
Beyer-Mears, A; Mistry, K; Diecke, F P et al. (1996) Zopolrestat prevention of proteinuria, albuminuria and cataractogenesis in diabetes mellitus. Pharmacology 52:292-302
Diecke, F P; Beyer-Mears, A; Mistry, K (1995) Kinetics of myo-inositol transport in rat ocular lens. J Cell Physiol 162:290-7
Mistry, K P; Beyer-Mears, A; Diecke, F P (1993) Mechanisms for D-glucose inhibition of myo-inositol influx into rat lens. Diabetes 42:1737-44
Beyer-Mears, A; Diecke, F P; Cruz, E et al. (1992) Myo-inositol transport in the lens of galactose-maintained rats. Curr Eye Res 11:25-34
Beyer-Mears, A; Murray, F T; Cruz, E et al. (1992) Comparison of sorbinil and ponalrestat (Statil) diminution of proteinuria in the BB rat. Pharmacology 45:285-91
Beyer-Mears, A; Bucci Jr, F A; Del Val, M et al. (1989) Dietary myo-inositol effect on sugar cataractogenesis. Pharmacology 39:59-68
Beyer-Mears, A; Murray, F T; Del Val, M et al. (1988) Reversal of proteinuria by sorbinil, an aldose reductase inhibitor in spontaneously diabetic (BB) rats. Pharmacology 36:112-20

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