Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1
Open Access
- 18 June 2013
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
- Vol. 2, e00324
- https://doi.org/10.7554/elife.00324
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
Funding Information
- National Eye Institute (NEI 5R01EY017950)
- RPB Physician-Scientist Award
- National Eye Institute (NEI 5R01EY20900)
- American Diabetes Association (ADA 1-10-BS-94)
- VA Merit Award
- Beckman Initiative for Macular Research (Grant 1003)
- Doris Duke Charitable Foundation
- Burroughs Wellcome Fund
- Ellison Medical Foundation
- National Eye Institute (NEI R01EY022238)
- National Eye Institute (NEI R01EY020672)
- Programme for Advanced Medical Education sponsored by Fundação Calouste Gulbenkian, Fundação Champalimaud, Ministério da Saúde, and Fundação para a Ciência e Tecnologia, Portugal
- National Natural Science Foundation of China
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