Marneros Alexander G, Keene Douglas R, Hansen Uwe, Fukai Naomi, Moulton Karen, Goletz Patrice L, Moiseyev Gennadiy, Pawlyk Basil S, Halfter Willi, Dong Sucai, Shibata Masao, Li Tiansen, Crouch Rosalie K, Bruckner Peter, Olsen Bjorn R
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
EMBO J. 2004 Jan 14;23(1):89-99. doi: 10.1038/sj.emboj.7600014. Epub 2003 Dec 11.
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.
视网膜色素上皮（RPE）下出现异常沉积物的年龄相关性黄斑变性（ARMD）是西方世界失明的主要原因。在早期ARMD中发现了基底膜沉积物，其由RPE产生的过量基底膜物质组成。在此，我们证明，缺乏基底膜成分胶原蛋白XVIII/内皮抑素的小鼠，其RPE下沉积物大量积累，与基底膜沉积物有惊人的相似之处，同时伴有RPE异常和年龄依赖性视力丧失。视觉功能的逐渐衰减是由于RPE中维生素A代谢异常导致视网膜视紫红质含量降低所致。此外，老年突变小鼠表现出光感受器异常，神经视网膜中胶质纤维酸性蛋白的表达增加。我们的数据表明，胶原蛋白XVIII/内皮抑素对RPE功能至关重要，并提示这种胶原蛋白在布鲁赫膜中起重要作用。与此作用一致，包括布鲁赫膜在内的基底膜中胶原蛋白XVIII/内皮抑素的超微结构组织表明，它是基底膜分子网络的一部分。
