Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1

Ling Luo, Hironori Uehara, Xiaohui Zhang, Subrata K. Das, Thomas Olsen, Derick Holt, Jacquelyn M. Simonis, Kyle Jackman, Nirbhai Singh, Tadashi R. Miya, Wei Huang, Faisal Ahmed, Ana Bastos-Carvalho, Yun Zheng Le, Christina Mamalis, Vince A. Chiodo, William W. Hauswirth, Judit Baffi, Pedro M. Lacal, Angela OrecchiaNapoleone Ferrara, Guangping Gao, Kim Young-hee, Yingbin Fu, Leah Owen, Romulo Albuquerque, Wolfgang Baehr, Kirk Thomas, Dean Y. Li, Kakarla V. Chalam, Masabumi Shibuya, Salvatore Grisanti, David J. Wilson, Jayakrishna Ambati, Balamurali K. Ambati

Research output: Contribution to journalArticlepeer-review

Abstract

Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life.

Original languageEnglish (US)
Article numbere00324
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Jun 18 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

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