Studies in the Lens and Cataract Biology Section are focussed on the biology of the normal lens and on elucidating mechanisms underlying the process of aging-related cataractogenesis. During the past year work has concentrated on aspects of signal transduction involving the Ras superfamily of small GTPases, proteins which act as molecular switches regulating many critical cellular functions. Dr. Qiu- fang Cheng has been working toward isolating and characterizing a novel group of GTP binding proteins which appear to be unique to lens fiber cells. We believe that these particular proteins may be involved in the process through which lens fibers differentiate from lens epithelial cells and ultimately become denucleated, mature fibers. In addition, we have been investigating the significance to lens functional integrity of isoprenylation, a post-synthetic modification essential for the proper function of most small GTPases. We have shown that blocking isoprenylation with different inhibitors causes cataract in model systems. Dr. Rachel Neal, who recently joined the Section, has initiated efforts to isolate an enzyme previously detected in the lens which utilizes the reducing equivalents of pyridine nucleotides to inactivate reactive oxygen species. This enzyme may be a primary part of the lens defense mechanisms against oxidative damage. - lens, cataract, aging, small GTPases,oxidative stress, isoprenoids

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000105-20
Application #
6290106
Study Section
Special Emphasis Panel (LMOD)
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
1999
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Gehlbach, P; Hose, S; Lei, B et al. (2006) Developmental abnormalities in the Nuc1 rat retina: a spontaneous mutation that affects neuronal and vascular remodeling and retinal function. Neuroscience 137:447-61
Smith, Amber A; Wyatt, Keith; Vacha, Jennifer et al. (2006) Gene duplication and separation of functions in alphaB-crystallin from zebrafish (Danio rerio). FEBS J 273:481-90
Jernigan Jr, Howard M; Blum, Penny S; Chakrabarti, Ipsit et al. (2005) Effects of cataractogenesis on the CDP-choline pathway: increased phospholipid synthesis in lenses from galactosemic rats and 13/N guinea pigs. Ophthalmic Res 37:7-12
Ghosh, Madhumita P; Zigler Jr, J Samuel (2005) Lack of fiber cell induction stops normal growth of rat lenses in organ culture. Mol Vis 11:901-8
Lizak, Martin J; Zigler Jr, J Samuel; Bettelheim, Frederick A (2005) Syneretic response to incremental pressures in calf lenses. Curr Eye Res 30:21-5
Neal, R E; Bettelheim, F A; Lin, C et al. (2005) Alterations in human vitreous humour following cataract extraction. Exp Eye Res 80:337-47
Zhang, Cheng; Gehlbach, Peter; Gongora, Celine et al. (2005) A potential role for beta- and gamma-crystallins in the vascular remodeling of the eye. Dev Dyn 234:36-47
Neal, R; Aykin-Burns, N; Ercal, N et al. (2005) Pb2+ exposure alters the lens alpha A-crystallin protein profile in vivo and induces cataract formation in lens organ culture. Toxicology 212:1-9
Hose, Stacey; Zigler Jr, J Samuel; Sinha, Debasish (2005) A novel rat model to study the functions of macrophages during normal development and pathophysiology of the eye. Immunol Lett 96:299-302
Rao, Ponugoti Vasantha; Maddala, Rupalatha; John, Faith et al. (2004) Expression of nonphagocytic NADPH oxidase system in the ocular lens. Mol Vis 10:112-21

Showing the most recent 10 out of 28 publications