Basement membrane abnormalities in human eyes with diabetic retinopathyAV Ljubimov, RE Burgeson, RJ Butkowski, JR Couchman, L Zardi, Y Ninomiya, Y Sado, ZS Huang, AB Nesburn and MC Kenney Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, UCLA Medical School Affiliate, Los Angeles, California 90048, USA. Vascular and parenchymal basement membranes (BMs) are thickened in diabetes, but alterations in individual BM components in diabetic eyes, especially in diabetic retinopathy (DR), are obscure. To identify abnormalities in the distribution of specific constituents, we analyzed cryostat sections of human eyes obtained at autopsy (seven normal, five diabetic without DR, and 13 diabetic with DR) by immunofluorescence with antibodies to 30 BM and extracellular matrix components. In non-DR eyes, no qualitative changes of ocular BM components were seen. In some DR corneas, epithelial BM was stained discontinuously for laminin-1, entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR corneas. Major BM alterations were found in DR retinas compared to normals and non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had accumulations of fibronectin (including cellular) and Types I, III, IV (alpha1-alpha2), and V collagen. The BM zone of new retinal blood vessels in neovascularized areas accumulated tenascin and Type XII collagen, whereas normal, diabetic, and adjacent DR retinas showed only weak and irregular staining. In preretinal membranes, perlecan, bamacan, and Types VI, VIII, XII, and XIV collagen were newly identified. Diabetic BM thickening appears to involve qualitative alterations of specific BM markers at an advanced disease stage, with the appearance of DR.
Volume 44,
Issue 12,
pp. 1469-1479,
12/01/1996
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T. L. Ponsioen, M. J. A. van Luyn, R. J. van der Worp, J. C. van Meurs, J. M. M. Hooymans, and L. I. Los Collagen Distribution in the Human Vitreoretinal Interface Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 4089 - 4095. [Abstract] [Full Text] [PDF] |
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R. J. Santulli, W. A. Kinney, S. Ghosh, B. L. DeCorte, L. Liu, R. W. A. Tuman, Z. Zhou, N. Huebert, S. E. Bursell, A. C. Clermont, et al. Studies with an Orally Bioavailable {alpha}V Integrin Antagonist in Animal Models of Ocular Vasculopathy: Retinal Neovascularization in Mice and Retinal Vascular Permeability in Diabetic Rats J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 894 - 901. [Abstract] [Full Text] [PDF] |
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H. Kaneko, K. M. Nishiguchi, M. Nakamura, S. Kachi, and H. Terasaki Retardation of Photoreceptor Degeneration in the Detached Retina of rd1 Mouse Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 781 - 787. [Abstract] [Full Text] [PDF] |
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M. Saghizadeh, A. A. Kramerov, J. Tajbakhsh, A. M. Aoki, C. Wang, N.-N. Chai, J. Y. Ljubimova, T. Sasaki, G. Sosne, M. R. J. Carlson, et al. Proteinase and Growth Factor Alterations Revealed by Gene Microarray Analysis of Human Diabetic Corneas Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3604 - 3615. [Abstract] [Full Text] [PDF] |
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W. Halfter, S. Dong, B. Schurer, C. Ring, G. J. Cole, and A. Eller Embryonic Synthesis of the Inner Limiting Membrane and Vitreous Body Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 2202 - 2209. [Abstract] [Full Text] [PDF] |
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D. S. Wall, R. L. Gendron, W. V. Good, E. Miskiewicz, M. Woodland, K. Leblanc, and H. Paradis Conditional Knockdown of Tubedown-1 in Endothelial Cells Leads to Neovascular Retinopathy Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3704 - 3712. [Abstract] [Full Text] [PDF] |
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K Probst, R Fijnheer, P Schellekens, and A Rothova Intraocular and plasma levels of cellular fibronectin in patients with uveitis and diabetes mellitus Br. J. Ophthalmol., May 1, 2004; 88(5): 667 - 672. [Abstract] [Full Text] [PDF] |
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Z. A. Khan, M. Cukiernik, J. R. Gonder, and S. Chakrabarti Oncofetal Fibronectin in Diabetic Retinopathy Invest. Ophthalmol. Vis. Sci., January 1, 2004; 45(1): 287 - 295. [Abstract] [Full Text] [PDF] |
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S. Roy, T. Sato, G. Paryani, and R. Kao Downregulation of Fibronectin Overexpression Reduces Basement Membrane Thickening and Vascular Lesions in Retinas of Galactose-Fed Rats Diabetes, May 1, 2003; 52(5): 1229 - 1234. [Abstract] [Full Text] [PDF] |
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L Chen, N Miyamura, Y Ninomiya, and J T Handa Distribution of the collagen IV isoforms in human Bruch's membrane Br. J. Ophthalmol., February 1, 2003; 87(2): 212 - 215. [Abstract] [Full Text] [PDF] |
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M. Hangai, N. Kitaya, J. Xu, C. K. Chan, J. J. Kim, Z. Werb, S. J. Ryan, and P. C. Brooks Matrix Metalloproteinase-9-Dependent Exposure of a Cryptic Migratory Control Site in Collagen is Required before Retinal Angiogenesis Am. J. Pathol., October 1, 2002; 161(4): 1429 - 1437. [Abstract] [Full Text] [PDF] |
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R. Castellon, S. Caballero, H. K. Hamdi, S. R. Atilano, A. M. Aoki, R. W. Tarnuzzer, M. C. Kenney, M. B. Grant, and A. V. Ljubimov Effects of Tenascin-C on Normal and Diabetic Retinal Endothelial Cells in Culture Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2758 - 2766. [Abstract] [Full Text] [PDF] |
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R. L. Gendron, W. V. Good, L. C. Adams, and H. Paradis Suppressed Expression of Tubedown-1 in Retinal Neovascularization of Proliferative Diabetic Retinopathy Invest. Ophthalmol. Vis. Sci., November 1, 2001; 42(12): 3000 - 3007. [Abstract] [Full Text] [PDF] |
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J. Winkler and H. Lünsdorf Ultrastructure and Composition of Asteroid Bodies Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 902 - 907. [Abstract] [Full Text] |
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J. Cao, M. K. Mathews, D S. McLeod, C. Merges, L. M Hjelmeland, and G. A Lutty Angiogenic factors in human proliferative sickle cell retinopathy Br. J. Ophthalmol., July 1, 1999; 83(7): 838 - 846. [Abstract] [Full Text] |
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A. V. Ljubimov, Z.-s. Huang, G. H. Huang, R. E. Burgeson, D. Gullberg, J. H. Miner, Y. Ninomiya, Y. Sado, and M. C. Kenney Human Corneal Epithelial Basement Membrane and Integrin Alterations in Diabetes and Diabetic Retinopathy J. Histochem. Cytochem., September 1, 1998; 46(9): 1033 - 1042. [Abstract] [Full Text] |
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