The goal of this project is to identify the events involved in lens fiber cell differentiation and to use this information to understand the basis of lens cataract formation. We will purify to homogeneity and prepare antibodies against lentropin, a protein factor found in vitreous humor which causes embryonic lens epithelial cells differentiate into lens fiber cells. Lentropin has already been purified greater than 1,000X and its basis properties described. Antibodies to lentropin will be used to identify the cells responsible for secreting lentropin and to prepare antibody affinity columns for bulk purification of lentropin. Using labelled lentropin preparations, the lentropin receptor on lens epithelial cells will be identified and quantitated. Preliminary steps will be taken to characteriza and purify the receptor. When lentropin binds to lens epithelial cells there is a rapid stimultion of phospholipid methylation which appears essential for further fiber cell differentiation. Several agents which alter the metabolism of phospholipids or their fatty acid components can block lentropin-stimulated cell differentiation or cause differentiation in the absence of lentropin. The phospholipid metabolites resulting from lentropin stimulation will be identified, isolated and tested for their ability to affect fiber cell formation. Lens cell elongation during fiber differentiation appears to be caused by an increase in cell volume. The molecular mechanisms responsible for this volume regulation will be examined with respect to changes in transmembrane transport of small molecules and the role of protein synthesis in volume regulation. Since cell volume regulation plays an important role in lens fiber formation, changes in cell volume during x-ray cataract formation have been measured. Lens epithelial cells increase in volume prior to fiber cell swelling and cataract formation. The importance of this increase in volume will be determined by studies that will diminish the possible role of inflammation in this phenomonon. In addition, tests will be performed to establish whether damage to dividing epithelial cells for disruption of fiber cell differentiation is the primary cause of radiation cataracts.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004853-02
Application #
3259384
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
U.S. Uniformed Services University of Health Science
Department
Type
Schools of Medicine
DUNS #
City
Bethesda
State
MD
Country
United States
Zip Code
20814
Oltean, Alina; Huang, Jie; Beebe, David C et al. (2016) Tissue growth constrained by extracellular matrix drives invagination during optic cup morphogenesis. Biomech Model Mechanobiol 15:1405-1421
Huang, Jie; Liu, Ying; Filas, Benjamen et al. (2015) Negative and positive auto-regulation of BMP expression in early eye development. Dev Biol 407:256-64
Huang, Jie; Liu, Ying; Oltean, Alina et al. (2015) Bmp4 from the optic vesicle specifies murine retina formation. Dev Biol 402:119-26
Chen, Ziyan; Huang, Jie; Liu, Ying et al. (2014) FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands. Development 141:2691-701
Wolf, Louise; Harrison, Wilbur; Huang, Jie et al. (2013) Histone posttranslational modifications and cell fate determination: lens induction requires the lysine acetyltransferases CBP and p300. Nucleic Acids Res 41:10199-214
Li, Qi; Yan, Hong; Ding, Tian-Bing et al. (2013) Oxidative responses induced by pharmacologic vitreolysis and/or long-term hyperoxia treatment in rat lenses. Curr Eye Res 38:639-48
Xie, Qing; Yang, Ying; Huang, Jie et al. (2013) Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain. PLoS One 8:e54507
Almony, Arghavan; Holekamp, Nancy M; Bai, Fang et al. (2012) Small-gauge vitrectomy does not protect against nuclear sclerotic cataract. Retina 32:499-505
Wiley, Luke A; Rajagopal, Ramya; Dattilo, Lisa K et al. (2011) The tumor suppressor gene Trp53 protects the mouse lens against posterior subcapsular cataracts and the BMP receptor Acvr1 acts as a tumor suppressor in the lens. Dis Model Mech 4:484-95
Huang, Jie; Rajagopal, Ramya; Liu, Ying et al. (2011) The mechanism of lens placode formation: a case of matrix-mediated morphogenesis. Dev Biol 355:32-42

Showing the most recent 10 out of 73 publications