Continued experimental studies of the pathogenesis of ocular wound healing and traction retinal detachment (TRD) in the traumatized eye are proposed. Our focus is the inevitable inflammatory reaction of the eye to trauma and the hypothesis that the migration of circulating blood monocytes into the injured eye, and their transformation into macrophages, is a basic feature of the ocular response. The importance of macrophages in the development of TRD will be tested in several rabbit models involving, variously the injection of macrophages, whole blood, RBC or growth factors into the vitreous of normal eyes and of eyes with a standard wound. Experiments include studies of recruitment of labelled macrophages into the eye, studies in monocyte-depleted animals, quantitative studies of mitogenic and chemotactic factors in the vitreous in vivo and in vitro, and extensive studies on the morphology of the vitreoretinal interface in normal eyes using freeze-fracture, scanning electron microscopy and immunoelectron microscopic procedures. Our results will reveal the extent to which macrophage invasion of the wounded eye determines the development of intraocular cellular proliferation, membrane formation and TRD. It is hoped that the studies will also identify some aspects of the wound healing response that could be a target for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002061-14
Application #
3256472
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1978-02-01
Project End
1993-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
14
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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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