Function, Age-Related Expression and Molecular Characterization of PEDF, A Neurotrophic Serpin Secreted by Human RPE Cells
The retinal pigment epithelium (RPE) is a highly specialized neuroepithelium that develops in advance of and lies adjacent to the neural retina where it plays a critical role in retinal homeostasis. RPE cells are multifunctional in nature and have been compared to machropages (Elner et al., 1981, Young and Bok, 1969), oligodendrocytes (Steinberg and Wood, 1974), astrocytes (Immel and Steinberg, 1986), melanocytes (Feeny-Burns, 1980) and hepatocytes (Bok 1985). The unique geography of this singled-celled epithelial layer allows it to establish a definitive blood-retinal barrier (Cunha-Vaz 1979) and to function as a transporting ang absorbing epithelium (Miller and Steinberg 1982; Misfeldt et al., 1976). In the vertebrate retina, a closed, extracellular microenvironment exists that is bounded by the apical membrane of RPE cells distally and photoreceptor inner segments and Muller cell processes proximally. Tight junctions effectively isolates if from most larger blood components and it is thought that most of the IPM components are synthesized by surroundings cells. This highly specialized matrix constitutes a novel conduit for the transfort nutrients, metabolites or trophic factors between the two cell layers and also facilities intercellular communication. Thus, analysis of the IPM is of importance because it contributes to our understanding of essentials aspects of retinal development, homeostasis and visual function. RPE cells from a functional complex with photoreceptor neurons of the retina and interacts with them through IPM. Cultured RPE cells synthesize and secrete several trophic factors including a photoreceptor-survival promoting factor (PSPA) (Hewitt et al., 1990), PDGF (Campochairo 1988), FGF (Plouet 1988), TGF-α (Fassio et al., 1988) and TGF-β (Connor et al., 1988).
Unable to display preview. Download preview PDF.
- Connor T, Roberts A, Sporn M, Davis J, Glaser B (1988) RPE cells synthesize and release transforming growth factor-β, a modulator of endothelial cell growth and wound healing. Invest. Ophthalmol Vis. Sci. 29: 307–313.Google Scholar
- Fassio JB, Jumblatt MM, Barr CC, Georghegan TE, Eiferman RA, Schultz GS (1988) Invest. Ophtalmol. Vis. Sci. 29: 242–250.Google Scholar
- Feeney-Burns L (1988) The pigments of the retinal pigment epithelium. Curr Top Eye Res 2: 120–178.Google Scholar
- Greider CW (1990) Telomeres, telomerase and senescence. BioEssays 12: 363: 369.Google Scholar
- Guzzetta V, Franco B, Trask BJ, Zhang H, Saucedo-Cardena O, de Oca-Luna RM, Greenberg F, Chinault AC, Lupski JR, and Patel PI (1992) Somatic cell hybrids, sequence-tagged sites, simple repeat polymorphisms and yeast artificial chromosomes for physical and genetic mapping of proximal 17p. Genomics 13: 551–559.PubMedCrossRefGoogle Scholar
- Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC (1990). Telomere reduction in human colorectal carcinoma and with ageing. Nature 346: 866: 868.Google Scholar
- Hageman GS, Johnson LV (1991) Structure, composition and function of the retinal interphotoreceptor matrix. In Progress in Retinal Research. N. Osborne and G.J. Chader, editors. Pergamon Press, Oxford, England. 207–250.Google Scholar
- Pfeffer B (1990) Improved methodology for cell culture of human and monkey retinal pigment epithelium. In progress in Retinal Research. N. Osborne and G.J. Chader editors. Pergamon Press, Oxford UK. 251–291.Google Scholar
- Plouet J (1988) Implication of the binding of acidic and basic fibroblast growth factors (FGF) to photolysed rhodopsin in visual transduction.Invest Ophthalmol. Vis. Sci. 293: 106–114.Google Scholar
- Shapira M, Patston PA (1991) Serine protease inhibitors (Serpins) TCM 1, 146–151.Google Scholar
- Taniwaki T, Becerra SP, Chader GJ, Schwartz JP (1994) Neurotrophic effects of pigment epithelium-derived factor on cerebellar granule cells in culture. J Neurochem suppl) 25: 50.Google Scholar
- Tombran-Tink J, Rodriguez IR, Mazuruk K, Shivaram S, Li A, Chader G (1994) Structural Analysis of the gene for pigment epithelium differentiation (PEDF) factor. Invest. Ophthal. Vis. Sci. 35: 1312.Google Scholar
- Tombran-Tink J, Shivaram S, Chader G, Johnson LV, Bok D (1995) Expression, secretion and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. J. Neurosci. (in press).Google Scholar