The long-term objective of the proposed project is to identify cellular processes and stimulatory agents that promote intraocular diseases such as proliferative vitreoretinopathy (PVR) so that specific methods can be devised to prevent the pathology. In PVR, cells from retina (glia and RPE) form cellular membranes that can cause traction retinal detachments. Events similar to those in wound healing appear to contribute to PVR: inflammation, cell migration, proliferation, contraction and extracellular matrix (ECM) synthesis. Agents which stimulate these processes in the eye are not well known. The hypothesis of the project is that cell-cell and cell-matrix, interactions provide part of th stimulus for pathologic cell migration and proliferation.
The specific aims are: (1) to identify products of inflammatory cells (vitreal macrophages) which stimulate migration and proliferation, (2) to identify interactions between retinal glia and RPE that promote proliferation by analysis of secretory products and of cell contact, and (3) to identify the growth- and migration- modulating effects of cell type-specific ECMs. To achieve these goals, culture medium conditioned by vitreal macrophages and by retinal glia will be analyzed for known growth and chemotaxis effectors using chemical treatments, immunoligic analysis with specific antibodies, and bioassays for growth and chemotaxis. Degradation products resulting from the action of macrophage enzymes on vitreous proteins will also be bioassayed. Modulation of retinal cell growth by cell contact will be studied by: (1-) radioautographic assay of growth modulation by living, metabolicallycoupled cells, and (2) growth modulation by non- living plasma membranes. To study ECM effects, culture substrates or chemotaxis membranes will be precoated with ECMs deposited by retinal cells, then used in subsequent assays for growth and migration. It is expected that cell proliferation and migration will be potentiated by interactions among the cellular and matrix components of PVR tissue membranes. The significance of such a finding is that local cellular environments can profoundly effect processes resulting in vitreoretinal pathology.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004799-10
Application #
3259328
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1982-09-30
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1993-08-31
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
McKay, B S; Burke, J M (1994) Separation of phenotypically distinct subpopulations of cultured human retinal pigment epithelial cells. Exp Cell Res 213:85-92
Suson, J D; Burke, J M (1993) Modulation of sodium-potassium adenosine triphosphatase in cultured bovine retinal pigment epithelium by potassium. Invest Ophthalmol Vis Sci 34:694-8
Arrindell, E L; McKay, B S; Jaffe, G J et al. (1992) Modulation of potassium transport in cultured retinal pigment epithelium and retinal glial cells by serum and epidermal growth factor. Exp Cell Res 203:192-7
Burke, J M; Jaffe, G J; Brzeski, C M (1991) The effect of culture density and proliferation rate on the expression of ouabain-sensitive Na/K ATPase pumps in cultured human retinal pigment epithelium. Exp Cell Res 194:190-4
Williams, D F; Burke, J M (1990) Modulation of growth in retina-derived cells by extracellular matrices. Invest Ophthalmol Vis Sci 31:1717-23
Burke, J M (1989) Stimulation of DNA synthesis in human and bovine RPE by peptide growth factors: the response to TNF-alpha and EGF is dependent upon culture density. Curr Eye Res 8:1279-86
Burke, J M (1989) Growth in retinal glial cells in vitro is affected differentially by two types of cell contact-mediated interactions. Exp Cell Res 180:13-9
Jaffe, G J; Mieler, W F; Burke, J M et al. (1989) Photoablation of ocular melanoma with a high-powered argon endolaser. Arch Ophthalmol 107:113-8
Burke, J M; Soref, C (1988) Topographical variation in growth in cultured bovine retinal pigment epithelium. Invest Ophthalmol Vis Sci 29:1784-8
Lambrou, F H; Burke, J M; Aaberg, T M (1987) Effect of silicone oil on experimental traction retinal detachment. Arch Ophthalmol 105:1269-72

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