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. 2003;101:499–520.

Analysis of retinal pigment epithelium integrin expression and adhesion to aged submacular human Bruch's membrane.

Marco A Zarbin
PMCID: PMC1359002  PMID: 14971591

Abstract

PURPOSE: Uncultured aged retinal pigment epithelium (RPE) does not resurface aged Bruch's membrane after 24 hours in organ culture. These experiments assess whether culturing alters RPE integrin expression and resurfacing of Bruch's membrane. METHODS: RNA was isolated from uncultured and cultured RPE of aged adult donor and fetal eyes. Integrin subunit messenger RNA (mRNA) expression was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and semiquantitative analysis of the amplified products. Cell surface integrin expression was assessed using flow cytometry. Passaged cultured fetal RPE and primary cultured aged RPE were seeded onto Bruch's membrane, and resurfacing was assessed with scanning electron microscopy. RESULTS: Uncultured fetal RPE had low levels of alpha3 and beta5 mRNA compared to passaged cultured fetal RPE. Uncultured aged RPE had decreased alpha1-5 mRNA compared to primary cultured aged RPE. Cultured aged RPE had decreased beta4 and beta5 mRNA compared to passaged cultured fetal RPE. Flow cytometry confirmed the expression of alpha1-5, alphav, and beta1 protein on cultured fetal RPE and alpha1-3 and beta1 protein on cultured aged RPE. Twenty-four hours after seeding, cultured fetal and aged RPE resurfaced 99% +/- 1.3% and 76% +/- 22%, respectively, of aged submacular Bruch's membrane specimens from which native RPE had been debrided, exposing the native RPE basement membrane. Cultured fetal and aged RPE resurfaced 97% +/- 3.1% and 39% +/- 35%, respectively, of specimens in which the inner collagenous layer was exposed. CONCLUSIONS: Uncultured aged RPE has low amounts of integrin subunits that form receptors for laminin, fibronectin, and collagens. Culturing up-regulates integrins and promotes more efficient aged RPE attachment to and survival on aged Bruch's membrane.

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Selected References

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  1. Abe T., Tomita H., Kano T., Yoshida M., Ohashi T., Nakamura Y., Nishikawa S., Tamai M. Autologous iris pigment epithelial cell transplantation in monkey subretinal region. Curr Eye Res. 2000 Apr;20(4):268–275. [PubMed] [Google Scholar]
  2. Abe T., Yoshida M., Tomita H., Kano T., Nakagawa Y., Sato M., Wada Y., Fuse N., Yamada T., Tamai M. Functional analysis after auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration. Tohoku J Exp Med. 1999 Dec;189(4):295–305. doi: 10.1620/tjem.189.295. [DOI] [PubMed] [Google Scholar]
  3. Abe T., Yoshida M., Tomita H., Kano T., Sato M., Wada Y., Fuse N., Yamada T., Tamai M. Auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration: short-term results. Tohoku J Exp Med. 2000 May;191(1):7–20. doi: 10.1620/tjem.191.7. [DOI] [PubMed] [Google Scholar]
  4. Aisenbrey Sabine, Lafaut Bart A., Szurman Peter, Grisanti Salvatore, Lüke Christoph, Krott Ralf, Thumann Gabriele, Fricke Julia, Neugebauer Antje, Hilgers Ralf-Dieter. Macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration. Arch Ophthalmol. 2002 Apr;120(4):451–459. doi: 10.1001/archopht.120.4.451. [DOI] [PubMed] [Google Scholar]
  5. Algvere P. V., Berglin L., Gouras P., Sheng Y., Kopp E. D. Transplantation of RPE in age-related macular degeneration: observations in disciform lesions and dry RPE atrophy. Graefes Arch Clin Exp Ophthalmol. 1997 Mar;235(3):149–158. doi: 10.1007/BF00941722. [DOI] [PubMed] [Google Scholar]
  6. Algvere P. V., Berglin L., Gouras P., Sheng Y. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol. 1994 Dec;232(12):707–716. doi: 10.1007/BF00184273. [DOI] [PubMed] [Google Scholar]
  7. Algvere P. V., Gouras P., Dafgård Kopp E. Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD. Eur J Ophthalmol. 1999 Jul-Sep;9(3):217–230. doi: 10.1177/112067219900900310. [DOI] [PubMed] [Google Scholar]
  8. Anderson D. H., Guérin C. J., Erickson P. A., Stern W. H., Fisher S. K. Morphological recovery in the reattached retina. Invest Ophthalmol Vis Sci. 1986 Feb;27(2):168–183. [PubMed] [Google Scholar]
  9. Anderson D. H., Guérin C. J., Erickson P. A., Stern W. H., Fisher S. K. Morphological recovery in the reattached retina. Invest Ophthalmol Vis Sci. 1986 Feb;27(2):168–183. [PubMed] [Google Scholar]
  10. Anderson D. H., Guérin C. J., Matsumoto B., Pfeffer B. A. Identification and localization of a beta-1 receptor from the integrin family in mammalian retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1990 Jan;31(1):81–93. [PubMed] [Google Scholar]
  11. Anderson D. H., Stern W. H., Fisher S. K., Erickson P. A., Borgula G. A. The onset of pigment epithelial proliferation after retinal detachment. Invest Ophthalmol Vis Sci. 1981 Jul;21(1 Pt 1):10–16. [PubMed] [Google Scholar]
  12. Asthagiri A. R., Nelson C. M., Horwitz A. F., Lauffenburger D. A. Quantitative relationship among integrin-ligand binding, adhesion, and signaling via focal adhesion kinase and extracellular signal-regulated kinase 2. J Biol Chem. 1999 Sep 17;274(38):27119–27127. doi: 10.1074/jbc.274.38.27119. [DOI] [PubMed] [Google Scholar]
  13. Banks C. N., Hutton W. K. Blindness in New South Wales. An estimate of the prevalence and some of the contributing causes. Aust J Ophthalmol. 1981 Nov;9(4):285–288. doi: 10.1111/j.1442-9071.1981.tb00923.x. [DOI] [PubMed] [Google Scholar]
  14. Belkin A. M., Stepp M. A. Integrins as receptors for laminins. Microsc Res Tech. 2000 Nov 1;51(3):280–301. doi: 10.1002/1097-0029(20001101)51:3<280::AID-JEMT7>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  15. Benecke B. J., Ben-Ze'ev A., Penman S. The control of mRNA production, translation and turnover in suspended and reattached anchorage-dependent fibroblasts. Cell. 1978 Aug;14(4):931–939. doi: 10.1016/0092-8674(78)90347-1. [DOI] [PubMed] [Google Scholar]
  16. Benner Jeffrey D., Sunness Janet S., Ziegler Matthias D., Soltanian Jalal. Limited macular translocation for atrophic maculopathy. Arch Ophthalmol. 2002 May;120(5):586–591. doi: 10.1001/archopht.120.5.586. [DOI] [PubMed] [Google Scholar]
  17. Berger A. S., Kaplan H. J. Clinical experience with the surgical removal of subfoveal neovascular membranes. Short-term postoperative results. Ophthalmology. 1992 Jun;99(6):969–976. doi: 10.1016/s0161-6420(92)31869-x. [DOI] [PubMed] [Google Scholar]
  18. Berglin L., Gouras P., Sheng Y., Lavid J., Lin P. K., Cao H., Kjeldbye H. Tolerance of human fetal retinal pigment epithelium xenografts in monkey retina. Graefes Arch Clin Exp Ophthalmol. 1997 Feb;235(2):103–110. doi: 10.1007/BF00941738. [DOI] [PubMed] [Google Scholar]
  19. Binder Susanne, Stolba Ulrike, Krebs Ilse, Kellner Lukas, Jahn Christian, Feichtinger Hans, Povelka Margit, Frohner Ursula, Kruger Andreas, Hilgers Ralf-Dieter. Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study. Am J Ophthalmol. 2002 Feb;133(2):215–225. doi: 10.1016/s0002-9394(01)01373-3. [DOI] [PubMed] [Google Scholar]
  20. Brem R. B., Robbins S. G., Wilson D. J., O'Rourke L. M., Mixon R. N., Robertson J. E., Planck S. R., Rosenbaum J. T. Immunolocalization of integrins in the human retina. Invest Ophthalmol Vis Sci. 1994 Aug;35(9):3466–3474. [PubMed] [Google Scholar]
  21. Bressler N. M., Bressler S. B., Gragoudas E. S. Clinical characteristics of choroidal neovascular membranes. Arch Ophthalmol. 1987 Feb;105(2):209–213. doi: 10.1001/archopht.1987.01060020063030. [DOI] [PubMed] [Google Scholar]
  22. Bressler N. M., Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2. Arch Ophthalmol. 2001 Feb;119(2):198–207. [PubMed] [Google Scholar]
  23. Burke J. M., Skumatz C. M., Irving P. E., McKay B. S. Phenotypic heterogeneity of retinal pigment epithelial cells in vitro and in situ. Exp Eye Res. 1996 Jan;62(1):63–73. doi: 10.1006/exer.1996.0008. [DOI] [PubMed] [Google Scholar]
  24. Burridge K., Chrzanowska-Wodnicka M. Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol. 1996;12:463–518. doi: 10.1146/annurev.cellbio.12.1.463. [DOI] [PubMed] [Google Scholar]
  25. Burton T. C. Recovery of visual acuity after retinal detachment involving the macula. Trans Am Ophthalmol Soc. 1982;80:475–497. [PMC free article] [PubMed] [Google Scholar]
  26. Busk M., Pytela R., Sheppard D. Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein. J Biol Chem. 1992 Mar 25;267(9):5790–5796. [PubMed] [Google Scholar]
  27. Campochiaro P. A., Hackett S. F. Corneal endothelial cell matrix promotes expression of differentiated features of retinal pigmented epithelial cells: implication of laminin and basic fibroblast growth factor as active components. Exp Eye Res. 1993 Nov;57(5):539–547. doi: 10.1006/exer.1993.1158. [DOI] [PubMed] [Google Scholar]
  28. Campochiaro P. A., Jerdon J. A., Glaser B. M. The extracellular matrix of human retinal pigment epithelial cells in vivo and its synthesis in vitro. Invest Ophthalmol Vis Sci. 1986 Nov;27(11):1615–1621. [PubMed] [Google Scholar]
  29. Cary L. A., Han D. C., Polte T. R., Hanks S. K., Guan J. L. Identification of p130Cas as a mediator of focal adhesion kinase-promoted cell migration. J Cell Biol. 1998 Jan 12;140(1):211–221. doi: 10.1083/jcb.140.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Castellarin A. A., Nasir M. A., Sugino I. K., Zarbin M. A. Clinicopathological correlation of primary and recurrent choroidal neovascularisation following surgical excision in age related macular degeneration. Br J Ophthalmol. 1998 May;82(5):480–487. doi: 10.1136/bjo.82.5.480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Castellarin A. A., Nasir M., Sugino I. K., Zarbin M. A. Progressive presumed choriocapillaris atrophy after surgery for age-related macular degeneration. Retina. 1998;18(2):143–149. doi: 10.1097/00006982-199818020-00008. [DOI] [PubMed] [Google Scholar]
  32. Castellarin A. A., Sugino I. K., Vargas J. A., Parolini B., Lui G. M., Zarbin M. A. In vitro transplantation of fetal human retinal pigment epithelial cells onto human cadaver Bruch's membrane. Exp Eye Res. 1998 Jan;66(1):49–67. doi: 10.1006/exer.1997.0404. [DOI] [PubMed] [Google Scholar]
  33. Castillo B. V., Jr, del Cerro M., White R. M., Cox C., Wyatt J., Nadiga G., del Cerro C. Efficacy of nonfetal human RPE for photoreceptor rescue: a study in dystrophic RCS rats. Exp Neurol. 1997 Jul;146(1):1–9. doi: 10.1006/exnr.1997.6534. [DOI] [PubMed] [Google Scholar]
  34. Chakravarthy U., Houston R. F., Archer D. B. Treatment of age-related subfoveal neovascular membranes by teletherapy: a pilot study. Br J Ophthalmol. 1993 May;77(5):265–273. doi: 10.1136/bjo.77.5.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Chang S. H., Phelps P. C., Berezesky I. K., Ebersberger M. L., Jr, Trump B. F. Studies on the mechanisms and kinetics of apoptosis induced by microinjection of cytochrome c in rat kidney tubule epithelial cells (NRK-52E). Am J Pathol. 2000 Feb;156(2):637–649. doi: 10.1016/S0002-9440(10)64768-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Chen C. S., Mrksich M., Huang S., Whitesides G. M., Ingber D. E. Geometric control of cell life and death. Science. 1997 May 30;276(5317):1425–1428. doi: 10.1126/science.276.5317.1425. [DOI] [PubMed] [Google Scholar]
  37. Chen H. C., Guan J. L. Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10148–10152. doi: 10.1073/pnas.91.21.10148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Chen W., Joos T. O., Defoe D. M. Evidence for beta 1-integrins on both apical and basal surfaces of Xenopus retinal pigment epithelium. Exp Eye Res. 1997 Jan;64(1):73–84. doi: 10.1006/exer.1996.0183. [DOI] [PubMed] [Google Scholar]
  39. Chong N. H., Bird A. C. Alternative therapies in exudative age related macular degeneration. Br J Ophthalmol. 1998 Dec;82(12):1441–1443. doi: 10.1136/bjo.82.12.1441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Chu P. G., Grunwald G. B. Functional inhibition of retinal pigment epithelial cell-substrate adhesion with a monoclonal antibody against the beta 1 subunit of integrin. Invest Ophthalmol Vis Sci. 1991 May;32(6):1763–1769. [PubMed] [Google Scholar]
  41. Chu P., Grunwald G. B. Identification of the 2A10 antigen of retinal pigment epithelium as a beta 1 subunit of integrin. Invest Ophthalmol Vis Sci. 1991 May;32(6):1757–1762. [PubMed] [Google Scholar]
  42. Coffey P. J., Girman S., Wang S. M., Hetherington L., Keegan D. J., Adamson P., Greenwood J., Lund R. D. Long-term preservation of cortically dependent visual function in RCS rats by transplantation. Nat Neurosci. 2002 Jan;5(1):53–56. doi: 10.1038/nn782. [DOI] [PubMed] [Google Scholar]
  43. Crabb John W., Miyagi Masaru, Gu Xiaorong, Shadrach Karen, West Karen A., Sakaguchi Hirokazu, Kamei Motohiro, Hasan Azeem, Yan Lin, Rayborn Mary E. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A. 2002 Oct 21;99(23):14682–14687. doi: 10.1073/pnas.222551899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Crafoord S., Algvere P. V., Seregard S., Kopp E. D. Long-term outcome of RPE allografts to the subretinal space of rabbits. Acta Ophthalmol Scand. 1999 Jun;77(3):247–254. doi: 10.1034/j.1600-0420.1999.770301.x. [DOI] [PubMed] [Google Scholar]
  45. Das A., Frank R. N., Zhang N. L., Turczyn T. J. Ultrastructural localization of extracellular matrix components in human retinal vessels and Bruch's membrane. Arch Ophthalmol. 1990 Mar;108(3):421–429. doi: 10.1001/archopht.1990.01070050119045. [DOI] [PubMed] [Google Scholar]
  46. Day M. L., Foster R. G., Day K. C., Zhao X., Humphrey P., Swanson P., Postigo A. A., Zhang S. H., Dean D. C. Cell anchorage regulates apoptosis through the retinoblastoma tumor suppressor/E2F pathway. J Biol Chem. 1997 Mar 28;272(13):8125–8128. doi: 10.1074/jbc.272.13.8125. [DOI] [PubMed] [Google Scholar]
  47. Del Priore L. V., Kaplan H. J., Hornbeck R., Jones Z., Swinn M. Retinal pigment epithelial debridement as a model for the pathogenesis and treatment of macular degeneration. Am J Ophthalmol. 1996 Nov;122(5):629–643. doi: 10.1016/s0002-9394(14)70481-7. [DOI] [PubMed] [Google Scholar]
  48. Del Priore L. V., Kaplan H. J., Tezel T. H., Hayashi N., Berger A. S., Green W. R. Retinal pigment epithelial cell transplantation after subfoveal membranectomy in age-related macular degeneration: clinicopathologic correlation. Am J Ophthalmol. 2001 Apr;131(4):472–480. doi: 10.1016/s0002-9394(00)00850-3. [DOI] [PubMed] [Google Scholar]
  49. Del Priore L. V., Tezel T. H. Reattachment rate of human retinal pigment epithelium to layers of human Bruch's membrane. Arch Ophthalmol. 1998 Mar;116(3):335–341. doi: 10.1001/archopht.116.3.335. [DOI] [PubMed] [Google Scholar]
  50. Derman M. P., Chen J. Y., Spokes K. C., Songyang Z., Cantley L. G. An 11-amino acid sequence from c-met initiates epithelial chemotaxis via phosphatidylinositol 3-kinase and phospholipase C. J Biol Chem. 1996 Feb 23;271(8):4251–4255. doi: 10.1074/jbc.271.8.4251. [DOI] [PubMed] [Google Scholar]
  51. Derman M. P., Cunha M. J., Barros E. J., Nigam S. K., Cantley L. G. HGF-mediated chemotaxis and tubulogenesis require activation of the phosphatidylinositol 3-kinase. Am J Physiol. 1995 Jun;268(6 Pt 2):F1211–F1217. doi: 10.1152/ajprenal.1995.268.6.F1211. [DOI] [PubMed] [Google Scholar]
  52. Derman M. P., Toker A., Hartwig J. H., Spokes K., Falck J. R., Chen C. S., Cantley L. C., Cantley L. G. The lipid products of phosphoinositide 3-kinase increase cell motility through protein kinase C. J Biol Chem. 1997 Mar 7;272(10):6465–6470. doi: 10.1074/jbc.272.10.6465. [DOI] [PubMed] [Google Scholar]
  53. Desai V. N., Del Priore L. V., Kaplan H. J. Choriocapillaris atrophy after submacular surgery in presumed ocular histoplasmosis syndrome. Arch Ophthalmol. 1995 Apr;113(4):408–409. doi: 10.1001/archopht.1995.01100040023014. [DOI] [PubMed] [Google Scholar]
  54. Eckhart L., Bach J., Ban J., Tschachler E. Melanin binds reversibly to thermostable DNA polymerase and inhibits its activity. Biochem Biophys Res Commun. 2000 May 19;271(3):726–730. doi: 10.1006/bbrc.2000.2716. [DOI] [PubMed] [Google Scholar]
  55. Eide B. L., Turck C. W., Escobedo J. A. Identification of Tyr-397 as the primary site of tyrosine phosphorylation and pp60src association in the focal adhesion kinase, pp125FAK. Mol Cell Biol. 1995 May;15(5):2819–2827. doi: 10.1128/mcb.15.5.2819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Elner S. G., Elner V. M. The integrin superfamily and the eye. Invest Ophthalmol Vis Sci. 1996 Apr;37(5):696–701. [PubMed] [Google Scholar]
  57. Erickson P. A., Fisher S. K., Anderson D. H., Stern W. H., Borgula G. A. Retinal detachment in the cat: the outer nuclear and outer plexiform layers. Invest Ophthalmol Vis Sci. 1983 Jul;24(7):927–942. [PubMed] [Google Scholar]
  58. Ferris F. L., 3rd, Fine S. L., Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984 Nov;102(11):1640–1642. doi: 10.1001/archopht.1984.01040031330019. [DOI] [PubMed] [Google Scholar]
  59. Fine S. L., Berger J. W., Maguire M. G., Ho A. C. Age-related macular degeneration. N Engl J Med. 2000 Feb 17;342(7):483–492. doi: 10.1056/NEJM200002173420707. [DOI] [PubMed] [Google Scholar]
  60. Fisher S. K., Stone J., Rex T. S., Linberg K. A., Lewis G. P. Experimental retinal detachment: a paradigm for understanding the effects of induced photoreceptor degeneration. Prog Brain Res. 2001;131:679–698. doi: 10.1016/s0079-6123(01)31053-1. [DOI] [PubMed] [Google Scholar]
  61. Franke T. F., Kaplan D. R., Cantley L. C. PI3K: downstream AKTion blocks apoptosis. Cell. 1997 Feb 21;88(4):435–437. doi: 10.1016/s0092-8674(00)81883-8. [DOI] [PubMed] [Google Scholar]
  62. Freund K. B., Yannuzzi L. A., Sorenson J. A. Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol. 1993 Jun 15;115(6):786–791. doi: 10.1016/s0002-9394(14)73649-9. [DOI] [PubMed] [Google Scholar]
  63. Frisch S. M., Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994 Feb;124(4):619–626. doi: 10.1083/jcb.124.4.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Frisch S. M., Ruoslahti E. Integrins and anoikis. Curr Opin Cell Biol. 1997 Oct;9(5):701–706. doi: 10.1016/s0955-0674(97)80124-x. [DOI] [PubMed] [Google Scholar]
  65. Frisch S. M., Vuori K., Ruoslahti E., Chan-Hui P. Y. Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol. 1996 Aug;134(3):793–799. doi: 10.1083/jcb.134.3.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Fujii G. Y., Pieramici D. J., Humayun M. S., Schachat A. P., Reynolds S. M., Melia M., De Juan E., Jr Complications associated with limited macular translocation. Am J Ophthalmol. 2000 Dec;130(6):751–762. doi: 10.1016/s0002-9394(00)00771-6. [DOI] [PubMed] [Google Scholar]
  67. Fujii G. Y., de Juan E., Thomas M. A., Pieramici D. J., Humayun M. S., Au Eong K. G. Limited macular translocation for the management of subfoveal retinal pigment epithelial loss after submacular surgery. Am J Ophthalmol. 2001 Feb;131(2):272–275. doi: 10.1016/s0002-9394(00)00774-1. [DOI] [PubMed] [Google Scholar]
  68. Gass J. D. Biomicroscopic and histopathologic considerations regarding the feasibility of surgical excision of subfoveal neovascular membranes. Am J Ophthalmol. 1994 Sep 15;118(3):285–298. [PubMed] [Google Scholar]
  69. Gaur V., Agarwal N., Li L., Turner J. E. Maintenance of opsin and S-antigen gene expression in RCS dystrophic rats following RPE transplantation. Exp Eye Res. 1992 Jan;54(1):91–101. doi: 10.1016/0014-4835(92)90073-2. [DOI] [PubMed] [Google Scholar]
  70. Geller A. M., Sieving P. A. Assessment of foveal cone photoreceptors in Stargardt's macular dystrophy using a small dot detection task. Vision Res. 1993 Jul;33(11):1509–1524. doi: 10.1016/0042-6989(93)90144-l. [DOI] [PubMed] [Google Scholar]
  71. Giambernardi T. A., Rodeck U., Klebe R. J. Bovine serum albumin reverses inhibition of RT-PCR by melanin. Biotechniques. 1998 Oct;25(4):564–566. doi: 10.2144/98254bm03. [DOI] [PubMed] [Google Scholar]
  72. Giancotti F. G., Ruoslahti E. Integrin signaling. Science. 1999 Aug 13;285(5430):1028–1032. doi: 10.1126/science.285.5430.1028. [DOI] [PubMed] [Google Scholar]
  73. Goldbaum M. H., Madden K. A new perspective on Bruch's membrane and the retinal pigment epithelium. Br J Ophthalmol. 1982 Jan;66(1):17–25. doi: 10.1136/bjo.66.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Gouras P., Algvere P. Retinal cell transplantation in the macula: new techniques. Vision Res. 1996 Dec;36(24):4121–4125. doi: 10.1016/s0042-6989(96)00180-0. [DOI] [PubMed] [Google Scholar]
  75. Gouras P., Flood M. T., Kjedbye H., Bilek M. K., Eggers H. Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye. Curr Eye Res. 1985 Mar;4(3):253–265. doi: 10.3109/02713688509000857. [DOI] [PubMed] [Google Scholar]
  76. Green W. R., Enger C. Age-related macular degeneration histopathologic studies. The 1992 Lorenz E. Zimmerman Lecture. Ophthalmology. 1993 Oct;100(10):1519–1535. doi: 10.1016/s0161-6420(93)31466-1. [DOI] [PubMed] [Google Scholar]
  77. Green W. R., Key S. N., 3rd Senile macular degeneration: a histopathologic study. Trans Am Ophthalmol Soc. 1977;75:180–254. [PMC free article] [PubMed] [Google Scholar]
  78. Green W. R., McDonnell P. J., Yeo J. H. Pathologic features of senile macular degeneration. Ophthalmology. 1985 May;92(5):615–627. [PubMed] [Google Scholar]
  79. Grossniklaus H. E., Hutchinson A. K., Capone A., Jr, Woolfson J., Lambert H. M. Clinicopathologic features of surgically excised choroidal neovascular membranes. Ophthalmology. 1994 Jun;101(6):1099–1111. doi: 10.1016/s0161-6420(13)31216-0. [DOI] [PubMed] [Google Scholar]
  80. Guinebault C., Payrastre B., Racaud-Sultan C., Mazarguil H., Breton M., Mauco G., Plantavid M., Chap H. Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves specific interactions of p85 alpha with actin filaments and focal adhesion kinase. J Cell Biol. 1995 May;129(3):831–842. doi: 10.1083/jcb.129.3.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Gundersen D., Powell S. K., Rodriguez-Boulan E. Apical polarization of N-CAM in retinal pigment epithelium is dependent on contact with the neural retina. J Cell Biol. 1993 Apr;121(2):335–343. doi: 10.1083/jcb.121.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Handa J. T., Verzijl N., Matsunaga H., Aotaki-Keen A., Lutty G. A., te Koppele J. M., Miyata T., Hjelmeland L. M. Increase in the advanced glycation end product pentosidine in Bruch's membrane with age. Invest Ophthalmol Vis Sci. 1999 Mar;40(3):775–779. [PubMed] [Google Scholar]
  83. Hanks S. K., Calalb M. B., Harper M. C., Patel S. K. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8487–8491. doi: 10.1073/pnas.89.18.8487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. He S., Wang H. M., Ogden T. E., Ryan S. J. Transplantation of cultured human retinal pigment epithelium into rabbit subretina. Graefes Arch Clin Exp Ophthalmol. 1993 Dec;231(12):737–742. doi: 10.1007/BF00919290. [DOI] [PubMed] [Google Scholar]
  85. Henkind P., Gartner S. The relationship between retinal pigment epithelium and the choriocapillaris. Trans Ophthalmol Soc U K. 1983;103(Pt 4):444–447. [PubMed] [Google Scholar]
  86. Hergott G. J., Nagai H., Kalnins V. I. Inhibition of retinal pigment epithelial cell migration and proliferation with monoclonal antibodies against the beta 1 integrin subunit during wound healing in organ culture. Invest Ophthalmol Vis Sci. 1993 Aug;34(9):2761–2768. [PubMed] [Google Scholar]
  87. Heth C. A., Yankauckas M. A., Adamian M., Edwards R. B. Characterization of retinal pigment epithelial cells cultured on microporous filters. Curr Eye Res. 1987 Aug;6(8):1007–1019. doi: 10.3109/02713688709034872. [DOI] [PubMed] [Google Scholar]
  88. Ho T. C., Del Priore L. V. Reattachment of cultured human retinal pigment epithelium to extracellular matrix and human Bruch's membrane. Invest Ophthalmol Vis Sci. 1997 May;38(6):1110–1118. [PubMed] [Google Scholar]
  89. Holekamp N. M., Thomas M. A., Dickinson J. D., Valluri S. Surgical removal of subfoveal choroidal neovascularization in presumed ocular histoplasmosis: stability of early visual results. Ophthalmology. 1997 Jan;104(1):22–26. doi: 10.1016/s0161-6420(97)30367-4. [DOI] [PubMed] [Google Scholar]
  90. Hsu J. K., Thomas M. A., Ibanez H., Green W. R. Clinicopathologic studies of an eye after submacular membranectomy for choroidal neovascularization. Retina. 1995;15(1):43–52. doi: 10.1097/00006982-199515010-00009. [DOI] [PubMed] [Google Scholar]
  91. Hudson H. L., Frambach D. A., Lopez P. F. Relation of the functional and structural fundus changes after submacular surgery for neovascular age-related macular degeneration. Br J Ophthalmol. 1995 May;79(5):417–423. doi: 10.1136/bjo.79.5.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Hughes P. E., Pfaff M. Integrin affinity modulation. Trends Cell Biol. 1998 Sep;8(9):359–364. doi: 10.1016/s0962-8924(98)01339-7. [DOI] [PubMed] [Google Scholar]
  93. Hungerford J. E., Compton M. T., Matter M. L., Hoffstrom B. G., Otey C. A. Inhibition of pp125FAK in cultured fibroblasts results in apoptosis. J Cell Biol. 1996 Dec;135(5):1383–1390. doi: 10.1083/jcb.135.5.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Hussain Ali A., Rowe Lisa, Marshall John. Age-related alterations in the diffusional transport of amino acids across the human Bruch's-choroid complex. J Opt Soc Am A Opt Image Sci Vis. 2002 Jan;19(1):166–172. doi: 10.1364/josaa.19.000166. [DOI] [PubMed] [Google Scholar]
  95. Huttenlocher A., Palecek S. P., Lu Q., Zhang W., Mellgren R. L., Lauffenburger D. A., Ginsberg M. H., Horwitz A. F. Regulation of cell migration by the calcium-dependent protease calpain. J Biol Chem. 1997 Dec 26;272(52):32719–32722. doi: 10.1074/jbc.272.52.32719. [DOI] [PubMed] [Google Scholar]
  96. Hyman L. G., Lilienfeld A. M., Ferris F. L., 3rd, Fine S. L. Senile macular degeneration: a case-control study. Am J Epidemiol. 1983 Aug;118(2):213–227. doi: 10.1093/oxfordjournals.aje.a113629. [DOI] [PubMed] [Google Scholar]
  97. Hynes Richard O. Integrins: bidirectional, allosteric signaling machines. Cell. 2002 Sep 20;110(6):673–687. doi: 10.1016/s0092-8674(02)00971-6. [DOI] [PubMed] [Google Scholar]
  98. Ignatius M. J., Large T. H., Houde M., Tawil J. W., Barton A., Esch F., Carbonetto S., Reichardt L. F. Molecular cloning of the rat integrin alpha 1-subunit: a receptor for laminin and collagen. J Cell Biol. 1990 Aug;111(2):709–720. doi: 10.1083/jcb.111.2.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Ishida M., Lui G. M., Yamani A., Sugino I. K., Zarbin M. A. Culture of human retinal pigment epithelial cells from peripheral scleral flap biopsies. Curr Eye Res. 1998 Apr;17(4):392–402. doi: 10.1080/02713689808951220. [DOI] [PubMed] [Google Scholar]
  100. Jiang L. Q., Hamasaki D. Corneal electroretinographic function rescued by normal retinal pigment epithelial grafts in retinal degenerative Royal College of Surgeons rats. Invest Ophthalmol Vis Sci. 1994 Dec;35(13):4300–4309. [PubMed] [Google Scholar]
  101. Jiang L. Q., Jorquera M., Streilein J. W. Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts. Exp Eye Res. 1994 Jun;58(6):719–728. doi: 10.1006/exer.1994.1069. [DOI] [PubMed] [Google Scholar]
  102. Karwatowski W. S., Jeffries T. E., Duance V. C., Albon J., Bailey A. J., Easty D. L. Preparation of Bruch's membrane and analysis of the age-related changes in the structural collagens. Br J Ophthalmol. 1995 Oct;79(10):944–952. doi: 10.1136/bjo.79.10.944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Keely P. J., Westwick J. K., Whitehead I. P., Der C. J., Parise L. V. Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K. Nature. 1997 Dec 11;390(6660):632–636. doi: 10.1038/37656. [DOI] [PubMed] [Google Scholar]
  104. Klein R., Davis M. D., Magli Y. L., Segal P., Klein B. E., Hubbard L. The Wisconsin age-related maculopathy grading system. Ophthalmology. 1991 Jul;98(7):1128–1134. doi: 10.1016/s0161-6420(91)32186-9. [DOI] [PubMed] [Google Scholar]
  105. Klein R., Klein B. E., Linton K. L. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992 Jun;99(6):933–943. doi: 10.1016/s0161-6420(92)31871-8. [DOI] [PubMed] [Google Scholar]
  106. Klein Ronald, Klein Barbara E. K., Tomany Sandra C., Meuer Stacy M., Huang Guan-Hua. Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study. Ophthalmology. 2002 Oct;109(10):1767–1779. doi: 10.1016/s0161-6420(02)01146-6. [DOI] [PubMed] [Google Scholar]
  107. Korte G. E., Burns M. S., Bellhorn R. W. Epithelium-capillary interactions in the eye: the retinal pigment epithelium and the choriocapillaris. Int Rev Cytol. 1989;114:221–248. doi: 10.1016/s0074-7696(08)60862-1. [DOI] [PubMed] [Google Scholar]
  108. Korte G. E., Gerszberg T., Pua F., Henkind P. Choriocapillaris atrophy after experimental destruction of the retinal pigment epithelium in the rat. A study in thin sections and vascular casts. Acta Anat (Basel) 1986;127(3):171–175. doi: 10.1159/000146277. [DOI] [PubMed] [Google Scholar]
  109. Korte G. E., Pua F. Choriocapillaris regeneration in the rabbit: a study with vascular casts. Acta Anat (Basel) 1988;133(3):224–228. doi: 10.1159/000146644. [DOI] [PubMed] [Google Scholar]
  110. Korte G. E., Reppucci V., Henkind P. RPE destruction causes choriocapillary atrophy. Invest Ophthalmol Vis Sci. 1984 Oct;25(10):1135–1145. [PubMed] [Google Scholar]
  111. Kramer R. H., Marks N. Identification of integrin collagen receptors on human melanoma cells. J Biol Chem. 1989 Mar 15;264(8):4684–4688. [PubMed] [Google Scholar]
  112. Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Lai C. C., Gouras P., Doi K., Tsang S. H., Goff S. P., Ashton P. Local immunosuppression prolongs survival of RPE xenografts labeled by retroviral gene transfer. Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3134–3141. [PubMed] [Google Scholar]
  114. Lambert H. M., Capone A., Jr, Aaberg T. M., Sternberg P., Jr, Mandell B. A., Lopez P. F. Surgical excision of subfoveal neovascular membranes in age-related macular degeneration. Am J Ophthalmol. 1992 Mar 15;113(3):257–262. doi: 10.1016/s0002-9394(14)71576-4. [DOI] [PubMed] [Google Scholar]
  115. Lappas A., Weinberger A. W., Foerster A. M., Kube T., Rezai K. A., Kirchhof B. Iris pigment epithelial cell translocation in exudative age-related macular degeneration. A pilot study in patients. Graefes Arch Clin Exp Ophthalmol. 2000 Aug;238(8):631–641. doi: 10.1007/s004170000149. [DOI] [PubMed] [Google Scholar]
  116. Lavail M. M., Li L., Turner J. E., Yasumura D. Retinal pigment epithelial cell transplantation in RCS rats: normal metabolism in rescued photoreceptors. Exp Eye Res. 1992 Oct;55(4):555–562. doi: 10.1016/s0014-4835(05)80168-x. [DOI] [PubMed] [Google Scholar]
  117. Leibowitz H. M., Krueger D. E., Maunder L. R., Milton R. C., Kini M. M., Kahn H. A., Nickerson R. J., Pool J., Colton T. L., Ganley J. P. The Framingham Eye Study monograph: An ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973-1975. Surv Ophthalmol. 1980 May-Jun;24(Suppl):335–610. [PubMed] [Google Scholar]
  118. Lewis H. Macular translocation with chorioscleral outfolding: a pilot clinical study. Am J Ophthalmol. 2001 Aug;132(2):156–163. doi: 10.1016/s0002-9394(01)01088-1. [DOI] [PubMed] [Google Scholar]
  119. Li L. X., Turner J. E. Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation. Exp Eye Res. 1988 Dec;47(6):911–917. doi: 10.1016/0014-4835(88)90073-5. [DOI] [PubMed] [Google Scholar]
  120. Li L. X., Turner J. E. Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and long-term survival characteristics. Exp Eye Res. 1988 Nov;47(5):771–785. doi: 10.1016/0014-4835(88)90044-9. [DOI] [PubMed] [Google Scholar]
  121. Li L., Turner J. E. Optimal conditions for long-term photoreceptor cell rescue in RCS rats: the necessity for healthy RPE transplants. Exp Eye Res. 1991 Jun;52(6):669–679. doi: 10.1016/0014-4835(91)90019-b. [DOI] [PubMed] [Google Scholar]
  122. Little C. W., Castillo B., DiLoreto D. A., Cox C., Wyatt J., del Cerro C., del Cerro M. Transplantation of human fetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina. Invest Ophthalmol Vis Sci. 1996 Jan;37(1):204–211. [PubMed] [Google Scholar]
  123. Liu S. Y., Redmond T. M. Role of the 3'-untranslated region of RPE65 mRNA in the translational regulation of the RPE65 gene: identification of a specific translation inhibitory element. Arch Biochem Biophys. 1998 Sep 1;357(1):37–44. doi: 10.1006/abbi.1998.0817. [DOI] [PubMed] [Google Scholar]
  124. Liversidge J., Sewell H. F., Thomson A. W., Forrester J. V. Lymphokine-induced MHC class II antigen expression on cultured retinal pigment epithelial cells and the influence of cyclosporin A. Immunology. 1988 Feb;63(2):313–317. [PMC free article] [PubMed] [Google Scholar]
  125. Lopez P. F., Grossniklaus H. E., Lambert H. M., Aaberg T. M., Capone A., Jr, Sternberg P., Jr, L'Hernault N. Pathologic features of surgically excised subretinal neovascular membranes in age-related macular degeneration. Am J Ophthalmol. 1991 Dec 15;112(6):647–656. doi: 10.1016/s0002-9394(14)77270-8. [DOI] [PubMed] [Google Scholar]
  126. Lopez R., Gouras P., Kjeldbye H., Sullivan B., Reppucci V., Brittis M., Wapner F., Goluboff E. Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. Invest Ophthalmol Vis Sci. 1989 Mar;30(3):586–588. [PubMed] [Google Scholar]
  127. Machemer R. Experimental retinal detachment in the owl monkey. IV. The reattached retina. Am J Ophthalmol. 1968 Dec;66(6):1075–1091. doi: 10.1016/0002-9394(68)90816-7. [DOI] [PubMed] [Google Scholar]
  128. Machemer R., Steinhorst U. H. Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration? Graefes Arch Clin Exp Ophthalmol. 1993 Nov;231(11):635–641. doi: 10.1007/BF00921957. [DOI] [PubMed] [Google Scholar]
  129. Mainster M. A., Reichel E. Transpupillary thermotherapy for age-related macular degeneration: long-pulse photocoagulation, apoptosis, and heat shock proteins. Ophthalmic Surg Lasers. 2000 Sep-Oct;31(5):359–373. [PubMed] [Google Scholar]
  130. Marks P. W., Hendey B., Maxfield F. R. Attachment to fibronectin or vitronectin makes human neutrophil migration sensitive to alterations in cytosolic free calcium concentration. J Cell Biol. 1991 Jan;112(1):149–158. doi: 10.1083/jcb.112.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  131. Marmorstein A. D., Bonilha V. L., Chiflet S., Neill J. M., Rodriguez-Boulan E. The polarity of the plasma membrane protein RET-PE2 in retinal pigment epithelium is developmentally regulated. J Cell Sci. 1996 Dec;109(Pt 13):3025–3034. doi: 10.1242/jcs.109.13.3025. [DOI] [PubMed] [Google Scholar]
  132. Marshall G. E., Konstas A. G., Reid G. G., Edwards J. G., Lee W. R. Collagens in the aged human macula. Graefes Arch Clin Exp Ophthalmol. 1994 Mar;232(3):133–140. doi: 10.1007/BF00176781. [DOI] [PubMed] [Google Scholar]
  133. Maruo T., Ikebukuro N., Kawanabe K., Kubota N. Changes in causes of visual handicaps in Tokyo. Jpn J Ophthalmol. 1991;35(3):268–272. [PubMed] [Google Scholar]
  134. McKay B. S., Burke J. M. Separation of phenotypically distinct subpopulations of cultured human retinal pigment epithelial cells. Exp Cell Res. 1994 Jul;213(1):85–92. doi: 10.1006/excr.1994.1176. [DOI] [PubMed] [Google Scholar]
  135. Meitinger D., Hunt D. M., Shih D. T., Fox J. C., Hunt R. C. Vitreous-induced modulation of integrins in retinal pigment epithelial cells: effects of fibroblast growth factor-2. Exp Eye Res. 2001 Nov;73(5):681–692. doi: 10.1006/exer.2001.1079. [DOI] [PubMed] [Google Scholar]
  136. Meredith J. E., Jr, Fazeli B., Schwartz M. A. The extracellular matrix as a cell survival factor. Mol Biol Cell. 1993 Sep;4(9):953–961. doi: 10.1091/mbc.4.9.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  137. Merrill P. T., LoRusso F. J., Lomeo M. D., Saxe S. J., Khan M. M., Lambert H. M. Surgical removal of subfoveal choroidal neovascularization in age-related macular degeneration. Ophthalmology. 1999 Apr;106(4):782–789. doi: 10.1016/S0161-6420(99)90167-7. [DOI] [PubMed] [Google Scholar]
  138. Mervin K., Valter K., Maslim J., Lewis G., Fisher S., Stone J. Limiting photoreceptor death and deconstruction during experimental retinal detachment: the value of oxygen supplementation. Am J Ophthalmol. 1999 Aug;128(2):155–164. doi: 10.1016/s0002-9394(99)00104-x. [DOI] [PubMed] [Google Scholar]
  139. Mitchell P., Smith W., Attebo K., Wang J. J. Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study. Ophthalmology. 1995 Oct;102(10):1450–1460. doi: 10.1016/s0161-6420(95)30846-9. [DOI] [PubMed] [Google Scholar]
  140. Moisseiev J., Alhalel A., Masuri R., Treister G. The impact of the macular photocoagulation study results on the treatment of exudative age-related macular degeneration. Arch Ophthalmol. 1995 Feb;113(2):185–189. doi: 10.1001/archopht.1995.01100020069031. [DOI] [PubMed] [Google Scholar]
  141. Moore D. J., Clover G. M. The effect of age on the macromolecular permeability of human Bruch's membrane. Invest Ophthalmol Vis Sci. 2001 Nov;42(12):2970–2975. [PubMed] [Google Scholar]
  142. Moore D. J., Hussain A. A., Marshall J. Age-related variation in the hydraulic conductivity of Bruch's membrane. Invest Ophthalmol Vis Sci. 1995 Jun;36(7):1290–1297. [PubMed] [Google Scholar]
  143. Mousa S. A., Lorelli W., Campochiaro P. A. Role of hypoxia and extracellular matrix-integrin binding in the modulation of angiogenic growth factors secretion by retinal pigmented epithelial cells. J Cell Biochem. 1999 Jul 1;74(1):135–143. [PubMed] [Google Scholar]
  144. Nasir M. A., Sugino I., Zarbin M. A. Decreased choriocapillaris perfusion following surgical excision of choroidal neovascular membranes in age-related macular degeneration. Br J Ophthalmol. 1997 Jun;81(6):481–489. doi: 10.1136/bjo.81.6.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  145. Ohji M., Mandarino L., SundarRaj N., Thoft R. A. Corneal epithelial cell attachment with endogenous laminin and fibronectin. Invest Ophthalmol Vis Sci. 1993 Jul;34(8):2487–2492. [PubMed] [Google Scholar]
  146. Ormerod L. D., Puklin J. E., Frank R. N. Long-term outcomes after the surgical removal of advanced subfoveal neovascular membranes in age-related macular degeneration. Ophthalmology. 1994 Jul;101(7):1201–1210. doi: 10.1016/s0161-6420(94)31200-0. [DOI] [PubMed] [Google Scholar]
  147. Ozaki S., Kita M., Yamana T., Negi A., Honda Y. Influence of the sensory retina on healing of the rabbit retinal pigment epithelium. Curr Eye Res. 1997 Apr;16(4):349–358. doi: 10.1076/ceyr.16.4.349.10696. [DOI] [PubMed] [Google Scholar]
  148. Pauleikhoff D., Harper C. A., Marshall J., Bird A. C. Aging changes in Bruch's membrane. A histochemical and morphologic study. Ophthalmology. 1990 Feb;97(2):171–178. [PubMed] [Google Scholar]
  149. Pauleikhoff D., Harper C. A., Marshall J., Bird A. C. Aging changes in Bruch's membrane. A histochemical and morphologic study. Ophthalmology. 1990 Feb;97(2):171–178. [PubMed] [Google Scholar]
  150. Paulsson M. Basement membrane proteins: structure, assembly, and cellular interactions. Crit Rev Biochem Mol Biol. 1992;27(1-2):93–127. doi: 10.3109/10409239209082560. [DOI] [PubMed] [Google Scholar]
  151. Penfold P. L., Gyory J. F., Hunyor A. B., Billson F. A. Exudative macular degeneration and intravitreal triamcinolone. A pilot study. Aust N Z J Ophthalmol. 1995 Nov;23(4):293–298. doi: 10.1111/j.1442-9071.1995.tb00179.x. [DOI] [PubMed] [Google Scholar]
  152. Peyman G. A., Blinder K. J., Paris C. L., Alturki W., Nelson N. C., Jr, Desai U. A technique for retinal pigment epithelium transplantation for age-related macular degeneration secondary to extensive subfoveal scarring. Ophthalmic Surg. 1991 Feb;22(2):102–108. [PubMed] [Google Scholar]
  153. Peyman G. A., Blinder K. J., Paris C. L., Alturki W., Nelson N. C., Jr, Desai U. A technique for retinal pigment epithelium transplantation for age-related macular degeneration secondary to extensive subfoveal scarring. Ophthalmic Surg. 1991 Feb;22(2):102–108. [PubMed] [Google Scholar]
  154. Philp N. J., Nachmias V. T. Polarized distribution of integrin and fibronectin in retinal pigment epithelium. Invest Ophthalmol Vis Sci. 1987 Aug;28(8):1275–1280. [PubMed] [Google Scholar]
  155. Pieramici D. J., De Juan E., Jr, Fujii G. Y., Reynolds S. M., Melia M., Humayun M. S., Schachat A. P., Hartranft C. D. Limited inferior macular translocation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Am J Ophthalmol. 2000 Oct;130(4):419–428. doi: 10.1016/s0002-9394(00)00533-x. [DOI] [PubMed] [Google Scholar]
  156. Pollack J. S., Del Priore L. V., Smith M. E., Feiner M. A., Kaplan H. J. Postoperative abnormalities of the choriocapillaris in exudative age-related macular degeneration. Br J Ophthalmol. 1996 Apr;80(4):314–318. doi: 10.1136/bjo.80.4.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  157. Pytela R., Pierschbacher M. D., Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. doi: 10.1016/0092-8674(85)90322-8. [DOI] [PubMed] [Google Scholar]
  158. Ramrattan R. S., van der Schaft T. L., Mooy C. M., de Bruijn W. C., Mulder P. G., de Jong P. T. Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging. Invest Ophthalmol Vis Sci. 1994 May;35(6):2857–2864. [PubMed] [Google Scholar]
  159. Rasmussen H., Chu K. W., Campochiaro P., Gehlbach P. L., Haller J. A., Handa J. T., Nguyen Q. D., Sung J. U. Clinical protocol. An open-label, phase I, single administration, dose-escalation study of ADGVPEDF.11D (ADPEDF) in neovascular age-related macular degeneration (AMD). Hum Gene Ther. 2001 Nov 1;12(16):2029–2032. [PubMed] [Google Scholar]
  160. Re F., Zanetti A., Sironi M., Polentarutti N., Lanfrancone L., Dejana E., Colotta F. Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells. J Cell Biol. 1994 Oct;127(2):537–546. doi: 10.1083/jcb.127.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  161. Reiske H. R., Kao S. C., Cary L. A., Guan J. L., Lai J. F., Chen H. C. Requirement of phosphatidylinositol 3-kinase in focal adhesion kinase-promoted cell migration. J Biol Chem. 1999 Apr 30;274(18):12361–12366. doi: 10.1074/jbc.274.18.12361. [DOI] [PubMed] [Google Scholar]
  162. Reiske H. R., Zhao J., Han D. C., Cooper L. A., Guan J. L. Analysis of FAK-associated signaling pathways in the regulation of cell cycle progression. FEBS Lett. 2000 Dec 15;486(3):275–280. doi: 10.1016/s0014-5793(00)02295-x. [DOI] [PubMed] [Google Scholar]
  163. Ren X. D., Kiosses W. B., Sieg D. J., Otey C. A., Schlaepfer D. D., Schwartz M. A. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J Cell Sci. 2000 Oct;113(Pt 20):3673–3678. doi: 10.1242/jcs.113.20.3673. [DOI] [PubMed] [Google Scholar]
  164. Rezai K. A., Kohen L., Wiedemann P., Heimann K. Iris pigment epithelium transplantation. Graefes Arch Clin Exp Ophthalmol. 1997 Sep;235(9):558–562. doi: 10.1007/BF00947084. [DOI] [PubMed] [Google Scholar]
  165. Rezai K. A., Lappas A., Kohen L., Wiedemann P., Heimann K. Comparison of tight junction permeability for albumin in iris pigment epithelium and retinal pigment epithelium in vitro. Graefes Arch Clin Exp Ophthalmol. 1997 Jan;235(1):48–55. doi: 10.1007/BF01007837. [DOI] [PubMed] [Google Scholar]
  166. Ridley A. J., Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992 Aug 7;70(3):389–399. doi: 10.1016/0092-8674(92)90163-7. [DOI] [PubMed] [Google Scholar]
  167. Rizzolo L. J. Basement membrane stimulates the polarized distribution of integrins but not the Na,K-ATPase in the retinal pigment epithelium. Cell Regul. 1991 Nov;2(11):939–949. doi: 10.1091/mbc.2.11.939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  168. Rizzolo L. J., Zhou S., Li Z. Q. The neural retina maintains integrins in the apical membrane of the RPE early in development. Invest Ophthalmol Vis Sci. 1994 Apr;35(5):2567–2576. [PubMed] [Google Scholar]
  169. Rosa R. H., Thomas M. A., Green W. R. Clinicopathologic correlation of submacular membranectomy with retention of good vision in a patient with age-related macular degeneration. Arch Ophthalmol. 1996 Apr;114(4):480–487. doi: 10.1001/archopht.1996.01100130476025. [DOI] [PubMed] [Google Scholar]
  170. Sakai Tsutomu, Calderone Jack B., Lewis Geoffrey P., Linberg Kenneth A., Fisher Steven K., Jacobs Gerald H. Cone photoreceptor recovery after experimental detachment and reattachment: an immunocytochemical, morphological, and electrophysiological study. Invest Ophthalmol Vis Sci. 2003 Jan;44(1):416–425. doi: 10.1167/iovs.02-0633. [DOI] [PubMed] [Google Scholar]
  171. Sarks J. P., Sarks S. H., Killingsworth M. C. Evolution of geographic atrophy of the retinal pigment epithelium. Eye (Lond) 1988;2(Pt 5):552–577. doi: 10.1038/eye.1988.106. [DOI] [PubMed] [Google Scholar]
  172. Sarks J. P., Sarks S. H., Killingsworth M. C. Morphology of early choroidal neovascularisation in age-related macular degeneration: correlation with activity. Eye (Lond) 1997;11(Pt 4):515–522. doi: 10.1038/eye.1997.137. [DOI] [PubMed] [Google Scholar]
  173. Sarks S. H. Ageing and degeneration in the macular region: a clinico-pathological study. Br J Ophthalmol. 1976 May;60(5):324–341. doi: 10.1136/bjo.60.5.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  174. Sawada H., Furthmayr H., Konomi H., Nagai Y. Immunoelectronmicroscopic localization of extracellular matrix components produced by bovine corneal endothelial cells in vitro. Exp Cell Res. 1987 Jul;171(1):94–109. doi: 10.1016/0014-4827(87)90254-0. [DOI] [PubMed] [Google Scholar]
  175. Schaller M. D., Borgman C. A., Cobb B. S., Vines R. R., Reynolds A. B., Parsons J. T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. doi: 10.1073/pnas.89.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  176. Schaller M. D., Otey C. A., Hildebrand J. D., Parsons J. T. Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains. J Cell Biol. 1995 Sep;130(5):1181–1187. doi: 10.1083/jcb.130.5.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  177. Schraermeyer U., Kayatz P., Thumann G., Luther T. T., Szurman P., Kociok N., Bartz-Schmidt K. U. Transplantation of iris pigment epithelium into the choroid slows down the degeneration of photoreceptors in the RCS rat. Graefes Arch Clin Exp Ophthalmol. 2000 Dec;238(12):979–984. doi: 10.1007/s004170000194. [DOI] [PubMed] [Google Scholar]
  178. Schwartz M. A., Schaller M. D., Ginsberg M. H. Integrins: emerging paradigms of signal transduction. Annu Rev Cell Dev Biol. 1995;11:549–599. doi: 10.1146/annurev.cb.11.110195.003001. [DOI] [PubMed] [Google Scholar]
  179. Seaton A. D., Sheedlo H. J., Turner J. E. A primary role for RPE transplants in the inhibition and regression of neovascularization in the RCS rat. Invest Ophthalmol Vis Sci. 1994 Jan;35(1):162–169. [PubMed] [Google Scholar]
  180. Seaton A. D., Turner J. E. RPE transplants stabilize retinal vasculature and prevent neovascularization in the RCS rat. Invest Ophthalmol Vis Sci. 1992 Jan;33(1):83–91. [PubMed] [Google Scholar]
  181. Shaw L. M., Rabinovitz I., Wang H. H., Toker A., Mercurio A. M. Activation of phosphoinositide 3-OH kinase by the alpha6beta4 integrin promotes carcinoma invasion. Cell. 1997 Dec 26;91(7):949–960. doi: 10.1016/s0092-8674(00)80486-9. [DOI] [PubMed] [Google Scholar]
  182. Sheng Y., Gouras P., Cao H., Berglin L., Kjeldbye H., Lopez R., Rosskothen H. Patch transplants of human fetal retinal pigment epithelium in rabbit and monkey retina. Invest Ophthalmol Vis Sci. 1995 Feb;36(2):381–390. [PubMed] [Google Scholar]
  183. Sieg D. J., Hauck C. R., Ilic D., Klingbeil C. K., Schaefer E., Damsky C. H., Schlaepfer D. D. FAK integrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol. 2000 May;2(5):249–256. doi: 10.1038/35010517. [DOI] [PubMed] [Google Scholar]
  184. Sommer A., Tielsch J. M., Katz J., Quigley H. A., Gottsch J. D., Javitt J. C., Martone J. F., Royall R. M., Witt K. A., Ezrine S. Racial differences in the cause-specific prevalence of blindness in east Baltimore. N Engl J Med. 1991 Nov 14;325(20):1412–1417. doi: 10.1056/NEJM199111143252004. [DOI] [PubMed] [Google Scholar]
  185. Song M. K., Lui G. M. Propagation of fetal human RPE cells: preservation of original culture morphology after serial passage. J Cell Physiol. 1990 Apr;143(1):196–203. doi: 10.1002/jcp.1041430127. [DOI] [PubMed] [Google Scholar]
  186. Starita C., Hussain A. A., Pagliarini S., Marshall J. Hydrodynamics of ageing Bruch's membrane: implications for macular disease. Exp Eye Res. 1996 May;62(5):565–572. doi: 10.1006/exer.1996.0066. [DOI] [PubMed] [Google Scholar]
  187. Stenn K. S. Epibolin: a protein of human plasma that supports epithelial cell movement. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6907–6911. doi: 10.1073/pnas.78.11.6907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  188. Stenn K. S., Madri J. A., Tinghitella T., Terranova V. P. Multiple mechanisms of dissociated epidermal cell spreading. J Cell Biol. 1983 Jan;96(1):63–67. doi: 10.1083/jcb.96.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  189. Stoker M., O'Neill C., Berryman S., Waxman V. Anchorage and growth regulation in normal and virus-transformed cells. Int J Cancer. 1968 Sep 15;3(5):683–693. doi: 10.1002/ijc.2910030517. [DOI] [PubMed] [Google Scholar]
  190. Tezel T. H., Del Priore L. V., Kaplan H. J. Harvest and storage of adult human retinal pigment epithelial sheets. Curr Eye Res. 1997 Aug;16(8):802–809. doi: 10.1076/ceyr.16.8.802.8981. [DOI] [PubMed] [Google Scholar]
  191. Tezel T. H., Del Priore L. V. Reattachment to a substrate prevents apoptosis of human retinal pigment epithelium. Graefes Arch Clin Exp Ophthalmol. 1997 Jan;235(1):41–47. doi: 10.1007/BF01007836. [DOI] [PubMed] [Google Scholar]
  192. Tezel T. H., Del Priore L. V. Repopulation of different layers of host human Bruch's membrane by retinal pigment epithelial cell grafts. Invest Ophthalmol Vis Sci. 1999 Mar;40(3):767–774. [PubMed] [Google Scholar]
  193. Tezel T. H., Kaplan H. J., Del Priore L. V. Fate of human retinal pigment epithelial cells seeded onto layers of human Bruch's membrane. Invest Ophthalmol Vis Sci. 1999 Feb;40(2):467–476. [PubMed] [Google Scholar]
  194. Thomas M. A., Dickinson J. D., Melberg N. S., Ibanez H. E., Dhaliwal R. S. Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophthalmology. 1994 Aug;101(8):1384–1396. doi: 10.1016/s0161-6420(94)31172-9. [DOI] [PubMed] [Google Scholar]
  195. Thomas M. A., Grand M. G., Williams D. F., Lee C. M., Pesin S. R., Lowe M. A. Surgical management of subfoveal choroidal neovascularization. Ophthalmology. 1992 Jun;99(6):952–976. doi: 10.1016/s0161-6420(92)31888-3. [DOI] [PubMed] [Google Scholar]
  196. Thomas M. A., Kaplan H. J. Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome. Am J Ophthalmol. 1991 Jan 15;111(1):1–7. doi: 10.1016/s0002-9394(14)76888-6. [DOI] [PubMed] [Google Scholar]
  197. Thumann G., Aisenbrey S., Schraermeyer U., Lafaut B., Esser P., Walter P., Bartz-Schmidt K. U. Transplantation of autologous iris pigment epithelium after removal of choroidal neovascular membranes. Arch Ophthalmol. 2000 Oct;118(10):1350–1355. doi: 10.1001/archopht.118.10.1350. [DOI] [PubMed] [Google Scholar]
  198. Thumann G., Bartz-Schmidt K. U., El Bakri H., Schraermeyer U., Spee C., Cui J. Z., Hinton D. R., Ryan S. J., Heimann K. Transplantation of autologous iris pigment epithelium to the subretinal space in rabbits. Transplantation. 1999 Jul 27;68(2):195–201. doi: 10.1097/00007890-199907270-00006. [DOI] [PubMed] [Google Scholar]
  199. Thumann G. Development and cellular functions of the iris pigment epithelium. Surv Ophthalmol. 2001 Jan-Feb;45(4):345–354. doi: 10.1016/s0039-6257(00)00195-8. [DOI] [PubMed] [Google Scholar]
  200. Toth C. A., Freedman S. F. Macular translocation with 360-degree peripheral retinectomy impact of technique and surgical experience on visual outcomes. Retina. 2001;21(4):293–303. doi: 10.1097/00006982-200108000-00001. [DOI] [PubMed] [Google Scholar]
  201. Tsukahara I., Ninomiya S., Castellarin A., Yagi F., Sugino I. K., Zarbin M. A. Early attachment of uncultured retinal pigment epithelium from aged donors onto Bruch's membrane explants. Exp Eye Res. 2002 Feb;74(2):255–266. doi: 10.1006/exer.2001.1123. [DOI] [PubMed] [Google Scholar]
  202. Turksen K., Aubin J. E., Sodek J., Kalnins V. I. Localization of laminin, type IV collagen, fibronectin, and heparan sulfate proteoglycan in chick retinal pigment epithelium basement membrane during embryonic development. J Histochem Cytochem. 1985 Jul;33(7):665–671. doi: 10.1177/33.7.3159787. [DOI] [PubMed] [Google Scholar]
  203. Valmaggia Christophe, Ries Gerhard, Ballinari Pietro. Radiotherapy for subfoveal choroidal neovascularization in age-related macular degeneration: a randomized clinical trial. Am J Ophthalmol. 2002 Apr;133(4):521–529. doi: 10.1016/s0002-9394(02)01336-3. [DOI] [PubMed] [Google Scholar]
  204. Vingerling J. R., Dielemans I., Hofman A., Grobbee D. E., Hijmering M., Kramer C. F., de Jong P. T. The prevalence of age-related maculopathy in the Rotterdam Study. Ophthalmology. 1995 Feb;102(2):205–210. doi: 10.1016/s0161-6420(95)31034-2. [DOI] [PubMed] [Google Scholar]
  205. Wagner M., Benson M. T., Rennie I. G., MacNeil S. Effects of pharmacological modulation of intracellular signalling systems on retinal pigment epithelial cell attachment to extracellular matrix proteins. Curr Eye Res. 1995 May;14(5):373–384. doi: 10.3109/02713689508999935. [DOI] [PubMed] [Google Scholar]
  206. Wassell J., Ellis S., Burke J., Boulton M. Fluorescence properties of autofluorescent granules generated by cultured human RPE cells. Invest Ophthalmol Vis Sci. 1998 Jul;39(8):1487–1492. [PubMed] [Google Scholar]
  207. Weitzman J. B., Pasqualini R., Takada Y., Hemler M. E. The function and distinctive regulation of the integrin VLA-3 in cell adhesion, spreading, and homotypic cell aggregation. J Biol Chem. 1993 Apr 25;268(12):8651–8657. [PubMed] [Google Scholar]
  208. Whiteley S. J., Litchfield T. M., Coffey P. J., Lund R. D. Improvement of the pupillary light reflex of Royal College of Surgeons rats following RPE cell grafts. Exp Neurol. 1996 Jul;140(1):100–104. doi: 10.1006/exnr.1996.0120. [DOI] [PubMed] [Google Scholar]
  209. Wongpichedchai S., Weiter J. J., Weber P., Dorey C. K. Comparison of external and internal approaches for transplantation of autologous retinal pigment epithelium. Invest Ophthalmol Vis Sci. 1992 Nov;33(12):3341–3352. [PubMed] [Google Scholar]
  210. Yamamoto S., Du J., Gouras P., Kjeldbye H. Retinal pigment epithelial transplants and retinal function in RCS rats. Invest Ophthalmol Vis Sci. 1993 Oct;34(11):3068–3075. [PubMed] [Google Scholar]
  211. Yamamoto T., Yamashita H. Scanning electron microscopic observation of Bruch's membrane with the osmium tetroxide treatment. Br J Ophthalmol. 1989 Mar;73(3):162–167. doi: 10.1136/bjo.73.3.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  212. Zhang X., Bok D. Transplantation of retinal pigment epithelial cells and immune response in the subretinal space. Invest Ophthalmol Vis Sci. 1998 May;39(6):1021–1027. [PubMed] [Google Scholar]
  213. Zhang Z., Vuori K., Reed J. C., Ruoslahti E. The alpha 5 beta 1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6161–6165. doi: 10.1073/pnas.92.13.6161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  214. Zutter M. M., Santoro S. A. Widespread histologic distribution of the alpha 2 beta 1 integrin cell-surface collagen receptor. Am J Pathol. 1990 Jul;137(1):113–120. [PMC free article] [PubMed] [Google Scholar]
  215. el Dirini A. A., Wang H. M., Ogden T. E., Ryan S. J. Retinal pigment epithelium implantation in the rabbit: technique and morphology. Graefes Arch Clin Exp Ophthalmol. 1992;230(3):292–300. doi: 10.1007/BF00176307. [DOI] [PubMed] [Google Scholar]

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