The primary and long-term objective of the proposed investigation is to study the mechanism(s) of cataractogenesis and develop approaches to delay, eventually inhibit cataract development and regress opacities in progression. For the proposed studies two experimental rat models, galactose cataract and cataracts associated with hypertension will be used to fulfill our objectives. These models will provide significant and relevant information towards understanding cataract development in humans associated with two risk factors, diabetes and hypertension. The proposed study on galactose cataract is a logical extension of our current ongoing investigations. For hypertension model, salt-sensitive hypertensive Dahl rats with a significant incidence of cataract development will be used. Potent aldose reductase inhibitors and antioxidants will be used to study their effect on delaying, inhibiting and reversing galactose-induced alterations int he lens and cataract. Moreover, allopurinol, a drug used for gout therapy and postulated to promote galactose cataract development will be used to investigate its role as a co-factor in sugar cataractogenesis. Chronic and acute salt restriction approach will be used to study delay, inhibition and reversal of cataracts in salt-sensitive hypertensive rats. Morphological techniques involving light, transmission and scanning electron microscopy, ultrastructural cytochemistry and immunocytochemistry, and biochemical and molecular biology techniques will be used for this study. Using these approaches alterations in lens morphology, sites and level of enzyme activities (Na+-K+-ATPase, Ca2+-ATPase, acid phosphatase and arylsulfatase) will be evaluated in both models. In addition, for galactose model changes in the plasma membrane protein MP26, hexoses and polyo1 levels and gene expression for several proteins in the lens will be investigated. this study will contribute information of clinical significance towards understanding of cataractogenesis in human and potentially lead toward development of means to delay, inhibit and reverse opacities associated with diabetes and hypertension.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001680-18
Application #
2158192
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1979-06-01
Project End
1995-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
18
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Oakland University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Rochester
State
MI
Country
United States
Zip Code
48309
Unakar, N J; Tsui, J; Johnson, M (1997) Effect of pretreatment of germanium-132 on Na(+)-K(+)-ATPase and galactose cataracts. Curr Eye Res 16:832-7
Unakar, N J; Johnson, M; Tsui, J et al. (1995) Effect of germanium-132 on galactose cataracts and glycation in rats. Exp Eye Res 61:155-64
Unakar, N J; Bobrowski, W F; Tsui, J Y et al. (1993) Elemental studies in rat lens during galactose cataract reversal. Curr Eye Res 12:675-83
Unakar, N J; Tsui, J; Anthony, P et al. (1993) Aldose reductase inhibitors and galactose toxicity in neonatal and maternal rat lenses. J Ocul Pharmacol 9:341-53
Johnson, M J; Unakar, N J (1992) Alterations in lens permeability during galactose cataract development in rat. Lens Eye Toxic Res 9:93-113
Wen, Y; Shu, S; Unakar, N J et al. (1992) Expression of c-myc protooncogene in rat lens cells during development, maturation and reversal of galactose cataracts. Mol Cell Biochem 112:73-9
Unakar, N J; Tsui, J Y; Johnson, M J (1992) Effect of aldose reductase inhibitors on lenticular dulcitol level in galactose fed rats. J Ocul Pharmacol 8:199-212
Shi, S; Unakar, N J; Wen, Y et al. (1992) Transient elevation of aldose reductase mRNA in lens of rats developing galactose cataracts. Mol Cell Biochem 115:27-34
Unakar, N J; Johnson, M J; Hynes, K (1991) Permeability studies in neonatal rat lens epithelium. Lens Eye Toxic Res 8:75-99
Wen, Y; Shi, S T; Unakar, N J et al. (1991) Crystallin mRNA concentrations and distribution in lens of normal and galactosemic rats. Implications in development of sugar cataracts. Invest Ophthalmol Vis Sci 32:1638-47

Showing the most recent 10 out of 29 publications