UV light, radiation, poor nutrition, diabetes, steroid administration and estrogen deficiency have been associated with increased prevalence of cataracts. The goal of this laboratory is to determine expressed gene changes that are involved in cataract formation. Reverse transcriptase- polymerase chain reaction differential display (DD) is a technique that compares the levels of expressed genes between two conditions. This method has been used by our laboratory to analyze expressed gene differences in lenses of UVA-exposed guinea pigs. Guinea pigs exposed to 5 months of UVA light developed early signs of cataract, which included increased nuclear light scattering and a decrease in lens soluble proteins. By DD, two genes associated with neoplasia, EB1 and RIG (Regulated in Glioma), were found to be down regulated in UVA treated lenses. This data suggests that UVA stress in the lens is associated with malignant processes. Differential display has also been used to examine genes involved in protecting mouse lens cells from oxidative damage. Cells were conditioned to survive in high concentrations of hydrogen peroxide. Genes that were up regulated in these cells included glutathione peroxidase, catalase, reticulocalbin, and alphaB- crystallin. The altered expression of these genes is consistent with the function of these proteins in cellular stress response and defense. - cataract, UVA-light, oxidative stress, reverse transcriptase-polymerase chain reaction differential display

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000312-03
Application #
6290140
Study Section
Special Emphasis Panel (LMOD)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cox, Constance A; Amaral, Juan; Salloum, Rita et al. (2010) Doxycycline's effect on ocular angiogenesis: an in vivo analysis. Ophthalmology 117:1782-91
Chen, Zhengguang; John, Molykutty; Subramanian, Saradha et al. (2004) 17Beta-estradiol confers a protective effect against transforming growth factor-beta2-induced cataracts in female but not male lenses. Exp Eye Res 78:67-74
Dufour, Eric M; Nandrot, Emeline; Marchant, Dominique et al. (2003) Identification of novel genes and altered signaling pathways in the retinal pigment epithelium during the Royal College of Surgeons rat retinal degeneration. Neurobiol Dis 14:166-80
Darmanin, Connie; Iwata, Takeshi; Carper, Deborah A et al. (2003) Expression, purification and preliminary crystallographic analysis of human sorbitol dehydrogenase. Acta Crystallogr D Biol Crystallogr 59:558-60
Carper, D; John, M; Chen, Z et al. (2001) Gene expression analysis of an H(2)O(2)-resistant lens epithelial cell line. Free Radic Biol Med 31:90-7
Singh, S B; Malamas, M S; Hohman, T C et al. (2000) Molecular modeling of the aldose reductase-inhibitor complex based on the X-ray crystal structure and studies with single-site-directed mutants. J Med Chem 43:1062-70
Sun, J K; Iwata, T; Zigler Jr, J S et al. (2000) Differential gene expression in male and female rat lenses undergoing cataract induction by transforming growth factor-beta (TGF-beta). Exp Eye Res 70:169-81
Lichtstein, D; McGowan, M H; Russell, P et al. (2000) Digitalis and digitalislike compounds down-regulate gene expression of the intracellular signaling protein 14-3-3 in rat lens. Hypertens Res 23 Suppl:S51-3
Frederikse, P H; Zigler Jr, S J; Farnsworth, P N et al. (2000) Prion protein expression in mammalian lenses. Curr Eye Res 20:137-43
Carper, D A; Sun, J K; Iwata, T et al. (1999) Oxidative stress induces differential gene expression in a human lens epithelial cell line. Invest Ophthalmol Vis Sci 40:400-6

Showing the most recent 10 out of 12 publications