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

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.

Pubmed ID: 21844367


  • Jones A
  • Kumar S
  • Zhang N
  • Tong Z
  • Yang JH
  • Watt C
  • Anderson J
  • Amrita
  • Fillerup H
  • McCloskey M
  • Luo L
  • Yang Z
  • Ambati B
  • Marc R
  • Oka C
  • Zhang K
  • Fu Y


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 30, 2011

Associated Grants

  • Agency: BLRD VA, Id: I01 BX001898
  • Agency: NEI NIH HHS, Id: P30 EY014800
  • Agency: NEI NIH HHS, Id: R01 EY002576
  • Agency: NEI NIH HHS, Id: R01 EY018660
  • Agency: NEI NIH HHS, Id: R01 EY021374

Mesh Terms

  • Animals
  • Choroidal Neovascularization
  • Humans
  • Macular Degeneration
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Neovascularization, Pathologic
  • Pancreatic Elastase
  • Proteins
  • Retinal Pigment Epithelium
  • Serine Endopeptidases
  • Vascular Endothelial Growth Factor A