期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 35, 页码 14578-14583出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1102853108
关键词
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资金
- National Eye Institute/National Institutes of Health
- National Basic Research Program of China (973 Program) [2011CB510200]
- Chinese National 985 Project
- West China Hospital
- Veterans Administration Merit Award
- Nara Institute of Science and Technology
- Inamori Foundation
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Career Development Award
- Karl Kirchgessner Foundation
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. Wet AMD includes typical choroidal neovascularization (CNV) and polypoidal choroidal vasculopathy (PCV). The etiology and pathogenesis of CNV and PCV are not well understood. Genome-wide association studies have linked a multifunctional serine protease, HTRA1, to AMD. However, the precise role of HTRA1 in AMD remains elusive. By transgenically expressing human HTRA1 in mouse retinal pigment epithelium, we showed that increased HTRA1 induced cardinal features of PCV, including branching networks of choroidal vessels, polypoidal lesions, severe degeneration of the elastic laminae, and tunica media of choroidal vessels. In addition, HTRA1 mice displayed retinal pigment epithelium atrophy and photoreceptor degeneration. Senescent HTRA1 mice developed occult CNV, which likely resulted from the degradation of the elastic lamina of Bruch's membrane and up-regulation of VEGF. Our results indicate that increased HTRA1 is sufficient to cause PCV and is a significant risk factor for CNV.
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