Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice

Alex Jones, Sandeep Kumar, Ning Zhang, Zongzhong Tong, Jia Hui Yang, Carl Watt, James Anderson, [No Value] Amrita, Heather Fillerup, Manabu McCloskey, Ling Luo, Zhenglin Yang, Balamurali Ambati, Robert Marc, Chio Oka, Kang Zhang, Yingbin Fu

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14578-14583
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number35
DOIs
StatePublished - Aug 30 2011
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice'. Together they form a unique fingerprint.

Cite this