Article
- The EMBO Journal (2004) 23, 89 - 99
- doi:10.1038/sj.emboj.7600014
Published online: 11 December 2003
Subject Categories:
Collagen XVIII/endostatin is essential for vision and retinal pigment epithelial function
Alexander G Marneros1, Douglas R Keene2, Uwe Hansen3, Naomi Fukai1, Karen Moulton4, Patrice L Goletz5, Gennadiy Moiseyev5, Basil S Pawlyk6, Willi Halfter7, Sucai Dong7, Masao Shibata8, Tiansen Li6, Rosalie K Crouch5, Peter Bruckner3 and Bjorn R Olsen1
- Department of Cell Biology, Harvard Medical School, Boston, MA, USA
- Portland Research Center, Shriners Hospitals for Children, Portland, OR, USA
- Department of Physiological Chemistry and Pathophysiology, University of Münster, Münster, Germany
- Department of Surgery, Children's Hospital, Boston, MA, USA
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
- Massachusetts Eye and Ear Infirmary, Boston, MA, USA
- Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
- Medical & Biological Laboratories Co., Ina-City, Japan
Correspondence to:
Alexander G Marneros, Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA. Fax: +1 617 432 0638; E-mail: alexander_marneros@hms.harvard.edu or alexmarneros@hotmail.com
Received 11 April 2003; Accepted 15 October 2003
Abstract
Age-related macular degeneration (ARMD) with abnormal deposit formation under the retinal pigment epithelium (RPE) is the major cause of blindness in the Western world. basal laminar deposits are found in early ARMD and are composed of excess basement membrane material produced by the RPE. Here, we demonstrate that mice lacking the basement membrane component collagen XVIII/endostatin have massive accumulation of sub-RPE deposits with striking similarities to basal laminar deposits, abnormal RPE, and age-dependent loss of vision. The progressive attenuation of visual function results from decreased retinal rhodopsin content as a consequence of abnormal vitamin A metabolism in the RPE. In addition, aged mutant mice show photoreceptor abnormalities and increased expression of glial fibrillary acidic protein in the neural retina. Our data demonstrate that collagen XVIII/endostatin is essential for RPE function, and suggest an important role of this collagen in Bruch's membrane. Consistent with such a role, the ultrastructural organization of collagen XVIII/endostatin in basement membranes, including Bruch's membrane, shows that it is part of basement membrane molecular networks.
Keywords:
- age-related macular degeneration,
- collagen XVIII,
- endostatin,
- retinal pigment epithelium
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