Abstract | BACKGROUND: METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
|
Authors | Magali Saint-Geniez, Arindel S R Maharaj, Tony E Walshe, Budd A Tucker, Eiichi Sekiyama, Tomoki Kurihara, Diane C Darland, Michael J Young, Patricia A D'Amore |
Journal | PloS one
(PLoS One)
Vol. 3
Issue 11
Pg. e3554
( 2008)
ISSN: 1932-6203 [Electronic] United States |
PMID | 18978936
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
|
Chemical References |
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factor Receptor-2
|
Topics |
- Aging
(genetics, metabolism)
- Animals
- Apoptosis
(genetics)
- Autocrine Communication
(genetics, physiology)
- Cell Survival
(genetics)
- Lac Operon
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Photoreceptor Cells, Vertebrate
(metabolism, physiology)
- Retina
(metabolism, physiology)
- Retinal Neovascularization
(genetics, metabolism)
- Retinal Neurons
(metabolism, physiology)
- Vascular Endothelial Growth Factor A
(genetics, metabolism, physiology)
- Vascular Endothelial Growth Factor Receptor-2
(genetics, metabolism)
- Vision, Ocular
(genetics)
|