Active scatter factor (HGF/SF) in proliferative vitreoretinal disease

PURPOSE. Hepatocyte growth factor/scatter factor (HGF/SF) possesses mitogen ic, motogenic, and morphogenic properties and has recently been implicated in various retinal diseases. The role of HGF/SF in proliferative vitreoreti nal disease was investigated. METHODS. Sections of epiretinal membranes were stained immunohistochemicall y for cytokeratins, to identify HRPE cells, and for HGF/SF receptor (c-Met) . Cultured HRPE cells were stained for c-Met and investigated for shape cha nge in response to HGF/SF, by using image analysis. The dose-response relat ionship for HRPE cells to HGF/SF was investigated by a cell migration assay and the specificity of this response evaluated by a neutralization experim ent. Subretinal fluid (SRF) and vitreous from patients with retinal detachm ent and proliferative vitreoretinopathy (PVR) plus vitreous from eyes obtai ned after death, eyes with macular hole, and eyes with proliferative diabet ic retinopathy (PDR) were investigated for the presence of HGF/SF using an enzyme-linked immunosorbent assay (ELISA). HGF/SF activity was measured usi ng an MDCK eel scatter assay. RESULTS. HRPE cells in epiretinal membranes and in culture expressed c-Met. Cultured HRPE cells responded to HGF/SF by an epithelial-to-mesenchymal sh ape change and by cell migration, a response that increased with increasing concentrations of HGF/SF. This response was reduced in the presence of neu tralizing antibody. There was evidence of HGF/SF in increasing concentratio ns in more severe PVR and in PDR when measured by ELISA, and, conversely, t here was evidence of correspondingly decreasing HGF/SF activity when measur ed by MDCK cell scatter assay in these diseases. CONCLUSIONS. HGF/SF is present in normal and pathologic vitreous. HRPE cell s respond by shape change and cell migration to HGF/SF. Concentrations of H GF/SF increase in proliferative vitreoretinal disease and increase in turn with increased severity of the disease, but HGF/SF bioactivity decreases (c onsistent with activator depletion). These findings are consistent with the hypothesis that HGF/SF may play a role in the HRPE mesenchymal transformat ion that typifies PVR.