eLife (Jun 2013)
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 Orecchia,
- Napoleone 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
Affiliations
- Ling Luo
- Moran Eye Center, University of Utah, Salt Lake City, United States; Department of Ophthalmology, The 306th Hospital of PLA, Beijing, China
- Hironori Uehara
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Xiaohui Zhang
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Subrata K Das
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Thomas Olsen
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Derick Holt
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Jacquelyn M Simonis
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Kyle Jackman
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Nirbhai Singh
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Tadashi R Miya
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Wei Huang
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Faisal Ahmed
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Ana Bastos-Carvalho
- Ophthalmology and Visual Sciences, University of Kentucky, Lexington, United States
- Yun Zheng Le
- Department of Medicine and Harold Hamm Oklahoma Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, United States
- Christina Mamalis
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Vince A Chiodo
- Ophthalmology, University of Florida-Gainesville, Gainesville, United States
- William W Hauswirth
- Ophthalmology, University of Florida-Gainesville, Gainesville, United States
- Judit Baffi
- Ophthalmology and Visual Sciences, University of Kentucky, Lexington, United States
- Pedro M Lacal
- Laboratory of Molecular Oncology, IDI-IRCCS, Istituto Dermopatico dell’Immacolata-IRCCS, Rome, Italy
- Angela Orecchia
- Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell’Immacolata-IRCCS, Rome, Italy
- Napoleone Ferrara
- Pharmaceutical Research, Genentech, South San Francisco, United States
- Guangping Gao
- Gene Therapy Center, University of Massachusetts Medical School, Worcester, United States; Department of Internal Medicine, Division of Cardiology, University of Utah, Salt Lake City, United States
- Kim Young-hee
- Ophthalmology and Visual Sciences, University of Kentucky, Lexington, United States
- Yingbin Fu
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Leah Owen
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Romulo Albuquerque
- Ophthalmology and Visual Sciences, University of Kentucky, Lexington, United States
- Wolfgang Baehr
- Moran Eye Center, University of Utah, Salt Lake City, United States
- Kirk Thomas
- Department of Internal Medicine, Division of Cardiology, University of Utah, Salt Lake City, United States
- Dean Y Li
- Department of Internal Medicine, Division of Cardiology, University of Utah, Salt Lake City, United States
- Kakarla V Chalam
- Department of Ophthalmology, University of Florida, Jacksonville, Jacksonville, United States
- Masabumi Shibuya
- Molecular Oncology, Institute of Physiology and Medicine, Jobu University, Takasaki, Japan
- Salvatore Grisanti
- Ophthalmology, University of Luebeck, Luebeck, Germany
- David J Wilson
- Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, United States
- Jayakrishna Ambati
- Ophthalmology and Visual Sciences, University of Kentucky, Lexington, United States
- Balamurali K Ambati
- Moran Eye Center, University of Utah, Salt Lake City, United States
- DOI
- https://doi.org/10.7554/eLife.00324
- Journal volume & issue
-
Vol. 2
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.
Keywords
- age-related macular degeneration
- photoreceptor metabolism
- retinal vasculature
- soluble VEGF receptor-1
- vascular demarcation
- transgenic model
