Journal article
Endogenous VEGF is required for visual function: evidence for a survival role on müller cells and photoreceptors
PloS one, Vol.3(11), pp.e3554-e3554
2008
DOI: 10.1371/journal.pone.0003554
PMCID: PMC2571983
PMID: 18978936
Abstract
Vascular endothelial growth factor (VEGF) is well known for its role in normal and pathologic neovascularization. However, a growing body of evidence indicates that VEGF also acts on non-vascular cells, both developmentally as well as in the adult. In light of the widespread use of systemic and intraocular anti-VEGF therapies for the treatment of angiogenesis associated with tumor growth and wet macular degeneration, systematic investigation of the role of VEGF in the adult retina is critical. Using immunohistochemistry and Lac-Z reporter mouse lines, we report that VEGF is produced by various cells in the adult mouse retina and that VEGFR2, the primary signaling receptor, is also widely expressed, with strong expression by Müller cells and photoreceptors. Systemic neutralization of VEGF was accomplished in mice by adenoviral expression of sFlt1. After 14 days of VEGF neutralization, there was no effect on the inner and outer retina vasculature, but a significant increase in apoptosis of cells in the inner and outer nuclear layers. By four weeks, the increase in neural cell death was associated with reduced thickness of the inner and outer nuclear layers and a decline in retinal function as measured by electroretinograms. siRNA-based suppression of VEGF expression in a Müller cell line in vitro supports the existence of an autocrine role for VEGF in Müller cell survival. Similarly, the addition of exogenous VEGF to freshly isolated photoreceptor cells and outer-nuclear-layer explants demonstrated VEGF to be highly neuroprotective. These results indicate an important role for endogenous VEGF in the maintenance and function of adult retina neuronal cells and indicate that anti-VEGF therapies should be administered with caution.
Details
- Title: Subtitle
- Endogenous VEGF is required for visual function: evidence for a survival role on müller cells and photoreceptors
- Creators
- Magali Saint-Geniez - Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USAArindel S R MaharajTony E WalsheBudd A TuckerEiichi SekiyamaTomoki KuriharaDiane C DarlandMichael J YoungPatricia A D'Amore
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.3(11), pp.e3554-e3554
- DOI
- 10.1371/journal.pone.0003554
- PMID
- 18978936
- PMCID
- PMC2571983
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- United States
- Grant note
- EY05318 / NEI NIH HHS R01 EY005318 / NEI NIH HHS P30EY14104 / NEI NIH HHS P30 EY014104 / NEI NIH HHS EY015435 / NEI NIH HHS R01 EY015435 / NEI NIH HHS
- Language
- English
- Date published
- 2008
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980387802771
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