Abstract
Age-related macular degeneration (AMD) is the most frequent cause for blindness in older age. The most severe complication is the development of choroidal neovascularisation (CNV). The retinal pigment epithelium (RPE) plays an important role in the induction of angiogenesis in AMD (Glaser et al., 1985; Young, 1987; Morse et al., 1989; Bird, 1991) by secreting the majority of angiogenic factors (Kliffen et al., 1997). The most important angiogenic factor is VEGF (vascular endothelial growth factor). CNV membranes contain high amounts of VEGF and it is known that overexpression of VEGF in the RPE leads to choroidal neovascularisation (Schwesinger et al., 2001). In vitro and in situ investigations revealed several extracellular stimuli inducing secretion of angiogenic factors by the RPE. A major part takes a hypoxia-comparable situation in the area of soft drusen (Eagle, 1984). In consequence to this, VEGF and factors inducing the VEGF production are secreted by the RPE and the neuronal retina (D' Amore, 1994; Shima et al., 1995; Stone et al., 1995; Frank et al., 1996; Kliffen et al., 1997; Tanihara et al., 1997). VEGF secretion is stimulated by advanced-glycation endproducts (AGE) accumulating in CNV membranes, and also by vitronectin, the major extracellular matrix component in drusen (Hammes et al., 1996; Hageman et al., 1999). In addition, insulin-like growth factor-1 (IGF-1) secreted by the neuronal retina and tumour necrosis factor-a (TNFa) secreted by macrophages which migrate towards the retina during the development of the first blood vessels are known to induce VEGF secretion by RPE cells (Punglia et al., 1997; Oh et al., 1999).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bence-Hanulec, K.K., Marshall, J. and Blair, L.A., 2000, Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of the alphal subunit on a specific tyrosine residue, Neuron 27:121-31.
Bird, A.C., 1991, Doyne Lecture. Pathogenesis of retinal pigment epithelial detachment in the elderly; the relevance of Bruch's membrane change, Eye 5:1-12.
Bito, H., Deisseroth, K. and Tsien, R.W., 1996, CREB phosphorylation and dephosphorylation: a Ca2+- and stimulus duration-dependent switch for hippocampal gene expression, Cell 87:1203-14.
Catterall, W.A., 1998, Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release, Cell Calcium 24:307-23.
Catterall, W.A., 2000, Structure and regulation of voltage-gated Ca2+ channels, Annu Rev Cell Dev Biol 16:521-55.
D' Amore, P.A., 1994, Mechanisms of retinal and choroidal neovascularization, Invest Ophthalmol Vis Sci 35:3974-9.
Deisseroth, K., Heist, E.K. and Tsien, R.W., 1998, Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons, Nature 392:198-202.
Eagle, R.C., Jr., 1984, Mechanisms of maculopathy, Ophthalmology 91:613-25.
Frank, R.N., Amin, R., Eliott, D., Puklin, J.E. and Abrams, G.W., 1996, Basic fibroblast growth factor and vascular endothelial growth factor present in epiretinal and choroidal neovascular membranes., Am J Ophthalmology 122:393-403.
Glaser, B.M., Campochiaro, P.A., Davis, J.L., Jr. and Sato, M., 1985, Retinal pigment epithelial cells release an inhibitor of neovascularization, Arch Ophthalmol 103:1870-5.
Hageman, G.S., Mullins, R.F., Russell, S.R., Johnson, L.V. and Anderson, D.H., 1999, Vitronectin is a constituent of ocular drusen and the vitronectin gene is expressed in human retinal pigmented epithelial cells, FASEB J 13:477-84.
Hammes, H.P., Brownlee, M., Jonczyk, A., Sutter, A. and Preissner, K.T., 1996, Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization, Nat Med 2:529-33.
Hell, J.W., Westenbroek, R.E., Breeze, L.J., Wang, K.K.W., Chavkin, C. and Catterall, W.A., 1996, N-MethylD-aspartate receptor-induced proteolytic conversion of postsynaptic class C L-type calcium channels in hippocampal neurons., Proc Natl Acad Sci 93:3362-67.
Hell, J.W., Westenbroek, R.E., Warner, C., Ahlijanian, M.K., Prystay, W., Gilbert, M.M., Snutch, T.P. and Catterall, W.A., 1993, Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits, J Cell Biol 123:949-62.
Holmes, T.C., Fadool, D.A. and Levitan, I.B., 1996, Tyrosine phosphorylation of the Kv 1.3 potassium channel.,JNeurosci 16:158-190.
Hughes, B.A. and Steinberg, R.H., 1990, Voltage-dependent currents in isolated cells of the frog retinal pigment epithelium., J Physiol 428:273-97.
Hughes, B.A. and Takahira, M., 1996, Inwardly rectifying K+ currents in isolated human retinal pigment epithelial cells., Invest Ophthalmol Vis Sci 37:1125-1139.
Hughes, B.A., Takahira, M. and Segawa, Y., 1995, An outwardly rectifying K+ current active near resting potential in human retinal pigment epithelial cells., Am J Physiol 269:179-187.
Kliffen, M., Sharma, H.S., Mooy, C.M., Kerkvliet, S. and de Jong, P.T., 1997, Increased expression of angiogenic growth factors in age-related maculopathy, Brit J Ophthalmol 81:154-62.
Koike, H., Saito, H. and Matsuki, N., 1993, Effect of fibroblast growth factors on calcium currents in acutely isolated neuronal cells from rat ventromedial hypothalamus, Neurosci Lett 150:57-60.
Morse, L.S., Terrell, J. and Sidikaro, Y., 1989, Bovine retinal pigment epithelium promotes proliferation of choroidal endothelium in vitro, Arch Ophthalmo 1107:165-963.
Murphy, T.H., Worley, P.F. and Baraban, J.M., 1991, L-type voltage-sensitive calcium channels mediate synaptic activation of immediate early genes, Neuron 7:625-35.
Nelson, M.T., Patlak, J.B., Worley, J.F. and Standen, N.B., 1990, Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone., Am J Physiol 259:3-18.
Oh, H., Takagi, H., Takagi, C., Suzuma, K., Otani, A., Ishida, K., Matsumura, M., Ogura, Y. and Honda, Y., 1999, The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes, Invest Ophthalmol Vis Sci 40:1891-8.
Pinto, L.H. and Klumpp, D.J., 1998, Localization of potassium channels in the retina, Prog Retinal Eye Res 17:207-30.
Platzer, J., Engel, J., Schrott-Fischer, A., Stephan, K., Bova, S., Chen, H., Zheng, H. and Striessnig, J., 2000, Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels, Cell 102:89-97.
Premkumar, D.R., Adhikary, G., Overholt, J.L., Simonson, M.S., Cherniack, N.S. and Prabhakar, N.R., 2000a, Intracellular pathways linking hypoxia to activation of c-fos and AP-1, Adv Exp Med Biol 475:101-9.
Premlumar, D.R., Mishra, R.R., Overholt, J.L., Simonson, M.S., Cherniack, N.S. and Prabhakar, N.R., 2006, L-type Ca(2+) channel activation regulates induction of c-fos transcription by hypoxia, JAppl Physiol 88:1898-906.
Punglia, R.S., Lu, M., Hsu, J., Kuroki, M., Tolentino, M.J., Keough, K., Levy, A.P., Levy, N.S., Goldberg, M.A., RJ, D.A. and Adamis, A.P., 1997, Regulation of vascular endothelial growth factor expression by insulin-like growth factor I, Diabetes 46:1619-26.
Puro, D.G., Hwang, J.-J., Kwon, 0.-J. and Chin, H., 1996, Characterization of an L-type calcium channel expressed by human retinal Müller (glial) cells., Mol Brain Res 37:41-48.
Rosenthal, R., Thieme, H. and Strauss, O., 2001, Fibroblast growth factor receptor 2 (FGFR2) in brain neurons and retinal pigment epithelial cells act via stimulation of neuroendocrine L-type channels (Cav1.3).,FASEB J 15:970-97.
Schwesinger, C., Yee, C., Rohan, R.M., Joussen, A.M., Fernandez, A., Meyer, T.N., Poulaki, V., Ma, J.J., Redmond, T.M., Liu, S., Adamis, A.P. and RJ, D.A., 2001, Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium, Am JPathol 158:1161-72.
Shima, D.T., Adamis, A.P., Ferrara, N., Yeo, K.-T., Yea, T.-K., Allende, R., Folkman, J. and D'Amore, P.A., 1995, Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen., Mol Med 1:182-93.
Stone, J., Itin, A., Alon, T., Peer, J., Gnessin, H., Chan-Ling, T. and Keshet, E., 1995, Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia, J Neurosci 15:4738-47.
Strauss, O., Buss, F., Rosenthal, R., Fischer, D., Mergler, S., Stumpff, F. and Thieme, H., 2000, Activation of neuroendocrine L-type channels (alphalD subunits) in retinal pigment epithelial cells and brain neurons by pp6Oe're,Biochem Biophys Res Commun 270:806-10.
Strauß, O., Mergler, S. and Wiederholt, M., 1997, Regulation of L-type calcium channels by tyrosine kinase and protein kinase C in cultured rat and human retinal pigment epithelial cells., FASEB J11:859-867.
Strauß, O., Richard, G. and Wienrich, M., 1993, Voltage-dependent potassium currents in cultured human retinal pigment epithelial cells., Biochem Biophys Res Commun 191:775-81.
Strauss, O., Rosenthal, R., Dey, D., Beninde, J., Wollmann, G., Thieme, H. and Wiederholt, M., 2002, Protein kinase C determines the effect of tyrosine kinase on delayed rectifier K' channels in rat RPE cells, Invest Ophthalmol Vis Sci 43:1645-54.
Strauß, O., Weiser, T. and Wienrich, M., 1994, Potassium currents in cultured cells of the rat retinal pigment epithelium., Comp Biochem Physiol A Physiol 109A:975-83.
Summers, B.A., Overholt, J.L. and Prabhakar, N.R., 2000, Augmentation of L-type calcium current by hypoxia in rabbit carotid body glomus cells: evidence for a PKC-sensitive pathway,JNeurophysiol 84:1636-44.
Takahira, M. and Hughes, B.A., 1997, Isolated bovine retinal pigment epithelial cells express delayed rectifier type and M-type K' currents., Am J Physiol 273:790-803.
Tanihara, H., Inatani, M. and Honda, Y., 1997, Growth factors and their receptors in the retina and pigment epithelium, Prog Retinal Eye Res 16:271-301.
Tao, Q. and Kelly, M.E.M., 1995, Calcium-activated potassium current in cultured rabbit retinal pigment epithelial cells., Curr Eye Res 15:237-46.
Tao, Q., Rafuse, P.E. and Kelly, M.E.M., 1994, Potassium currents in cultured rabbit retinal pigment epithelial cells., J Membrane Biol 141:123-38.
Wijetunge, S. and Hughes, A.D., 1995, pp60c-src increases voltage-operated calcium channel currents in vascular smooth muscle cells., Biochem Biophys Res Commun 217:1039-44.
Wu, X., Mogford, J.E., Platts, S.H., Davis, G.E., Meininger, G.A. and Davis, M.J., 1998, Modulation of calcium current in arteriolar smooth muscle by alphav beta3 and alphas betal integrin ligands, JCell Biol 143:241-52.
Young, R.W., 1987, Pathophysiology of age-related macular degeneration, Sury Ophthalmol 31:291-306.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this paper
Cite this paper
Rosenthal, R., Strauß, O. (2003). Investigations of RPE Cells of Choriodal Neovascular Membranes from Patients with Age-Related Macula Degeneration. In: LaVail, M.M., Hollyfield, J.G., Anderson, R.E. (eds) Retinal Degenerations. Advances in Experimental Medicine and Biology, vol 533. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0067-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0067-4_14
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4909-9
Online ISBN: 978-1-4615-0067-4
eBook Packages: Springer Book Archive