Abstract

Continued studies of the role of the retinal pigment epithelium (RPE) in the pathogenesis of proliferative vitreoretinopathy (PVR) are proposed. Our recent studies suggest the importance of hepatocyte growth factor (HGF) and connective tissue growth factor (CTGF) in PVR. A new model of PVR pathogenesis will be tested which incorporates the following HYPOTHESES: (1) The formation of invasive multilayered groups of RPE from an intact monolayer is mediated in part by HGF expressed by RPE. (2) Transformation of cellular RPE membranes into densely fibrotic membranes is mediated in part by CTGF.
Specific Aims to test these hypotheses are: The cellular and molecular mechanisms by which (1) HGF stimulates the formation of multilayered groups of RPE from the monolayer, and (2) CTGF induces transformation of epiretinal membranes from cellular to fibrotic will be determined. (3) The effects of over-expression or inhibition of HGF and/or CTGF on the development of PVR invivo will be determined. Accomplishment of these aims may open new strategies of therapy for PVR, a blinding complication of eye injury or retinal detachment surgery.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002061-26
Application #
6641267
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Dudley, Peter A
Project Start
1978-02-01
Project End
2007-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
26
Fiscal Year
2003
Total Cost
$325,000
Indirect Cost

  Institution

Name
University of Southern California
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

Zhu, DanHong; Sreekumar, Parameswaran G; Hinton, David R et al. (2010) Expression and regulation of enzymes in the ceramide metabolic pathway in human retinal pigment epithelial cells and their relevance to retinal degeneration. Vision Res 50:643-51
He, Shikun; Kumar, S Ram; Zhou, Peng et al. (2010) Soluble EphB4 inhibition of PDGF-induced RPE migration in vitro. Invest Ophthalmol Vis Sci 51:543-52
Sreekumar, Parameswaran G; Ding, Yi; Ryan, Stephen J et al. (2009) Regulation of thioredoxin by ceramide in retinal pigment epithelial cells. Exp Eye Res 88:410-7
He, Shikun; Chen, Youxin; Khankan, Rima et al. (2008) Connective tissue growth factor as a mediator of intraocular fibrosis. Invest Ophthalmol Vis Sci 49:4078-88
Yaung, Jennifer; Kannan, Ram; Wawrousek, Eric F et al. (2008) Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia. Exp Eye Res 86:355-65
Yaung, Jennifer; Jin, Manlin; Barron, Ernesto et al. (2007) alpha-Crystallin distribution in retinal pigment epithelium and effect of gene knockouts on sensitivity to oxidative stress. Mol Vis 13:566-77
Gamulescu, Maria-Andreea; Chen, Youxin; He, Shikun et al. (2006) Transforming growth factor beta2-induced myofibroblastic differentiation of human retinal pigment epithelial cells: regulation by extracellular matrix proteins and hepatocyte growth factor. Exp Eye Res 83:212-22
Sreekumar, Parameswaran G; Kannan, Ram; Yaung, Jennifer et al. (2005) Protection from oxidative stress by methionine sulfoxide reductases in RPE cells. Biochem Biophys Res Commun 334:245-53
Jin, Manlin; Yaung, Jennifer; Kannan, Ram et al. (2005) Hepatocyte growth factor protects RPE cells from apoptosis induced by glutathione depletion. Invest Ophthalmol Vis Sci 46:4311-9
Hoffmann, Stephan; He, Shikun; Jin, Manlin et al. (2005) A selective cyclic integrin antagonist blocks the integrin receptors alphavbeta3 and alphavbeta5 and inhibits retinal pigment epithelium cell attachment, migration and invasion. BMC Ophthalmol 5:16

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