Proliferative vitreoretinopathy (PVR) is the leading cause of failure of retinal detachment surgery. It is characterized by an exaggerated ocular wound healing response that may ultimately lead to retinal detachment and loss of vision. Cytokines (also called growth factors) have been implicated as important mediators in the pathogenesis of PVR; however, little in known regarding the regulation of cytokine production in this disease. The long range goal of the project is to characterize the pattern of cytokine expression and production by retinal pigment epithelial cells in PVR. By defining the endogenous pattern of cytokine expression and production, the pathogenesis of PVR may be more clearly understood and specific treatment may then be tailored to prevent or treat this condition. Our working hypothesis is that retinal pigment epithelial cells, key cells in PVR, produce cytokines which contribute to the exaggerated wound healing response. We further postulate that cytokine production by retinal pigment epithelial cells in PVR differs from the pattern of cytokines that are produced normally. We will use the techniques of polymerase chain reaction (PCR) and quantitative protein immunoassay to determine the profile of cytokines expressed normally and under conditions simulating PVR. PCR and Nuclear run-off transcription assay will be used to gain insight into the mechanism of cytokine MRNA expression.
The specific aims are to determine the pattern of expression of the cytokines interleukin-1(IL-1), macrophage colony stimulating factor (M- CSF), and gro by retinal pigment epithelial cells in tissue culture in response to the following factors: I) Selected recombinant cytokines (e.g. IL-1beta and transforming growth factor beta) that may be important in the pathogenesis of PVR. II) Heterogeneous products found in vitrectomy fluid and conditioned media from retinal pigment epithelial cells, retinal glial cells and macrophages, key cells found in PVR membranes. III) Specific matrix macromolecules found in normal retinal pigment epithelial cell basement membrane, PVR membranes or vitrectomy fluid. These matrix macromolecules will include collagen Types I-IV, laminin, and fibronectin. IV) Hypoxia. V) Treatment with triamcinolone acetonide in combination with agents or conditions that induce cytokine expression, as determined in I-IV) above.
| Shattuck, R L; Wood, L D; Jaffe, G J et al. (1994) MGSA/GRO transcription is differentially regulated in normal retinal pigment epithelial and melanoma cells. Mol Cell Biol 14:791-802 |
