Abnormal migration and proliferation of human retinal pigment epithelial cells are closely associated with many severe ocular diseases, such as PVR, AMD, and PDR. Various growth factors as well as cytokines are upregulated in the vitreous cavity after destruction of blood retinal barrier. The purpose of this project is to examine the effect of different growth factors as well as cytokines on the migration and proliferation of human retinal pigment epithelial cells. ? ? All PDGF isoforms (PDGF-A, -B, -C and ?D) are expressed in human fetal retinal pigment epithelial cells (hfRPE). Both of two PDGF receptors, -alpha and -beta are localized to the apical membrane on hfRPE. PDGF BB, AB and DD significantly increased the migration of hfRPE, and PDGF BB, CC and DD significantly increased proliferation. A proinflammatory cytokine cocktail composed of TNFa, IL-1beta and IFN-gama completely inhibited the stimulatory effects of fetal bovine serum as well as PDGF BB-induced migration and proliferation of hfRPE. Annexin-V-Fluos analysis showed that the inflammatory cytokine cocktail induced apoptosis in hfRPE which partially explained the inhibiton effect of inflammatory cytokine cocktail. These results may help identify a set of pathways (eg, apoptosis) potentially important for mitigating the progression of growth factor mediated retinal degenerative diseases such as PVR and AMD.
| Illek, Beate; Fu, Zhu; Schwarzer, Christian et al. (2008) Flagellin-stimulated Cl- secretion and innate immune responses in airway epithelia: role for p38. Am J Physiol Lung Cell Mol Physiol 295:L531-42 |
| Li, Rong; Maminishkis, Arvydas; Wang, Fei E et al. (2007) PDGF-C and -D induced proliferation/migration of human RPE is abolished by inflammatory cytokines. Invest Ophthalmol Vis Sci 48:5722-32 |
