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.
Showing the most recent 10 out of 16 publications
