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Soluble VEGF isoforms are required for the maintenance of the retinal pigment epithelium (RPE)‐choriocapillaris complex in the adult
Author(s) -
Saintgeniez Magali,
Kurihara Tomoki,
Sekiyama Eiichi,
Maldonado Angel,
D'Amore Patricia
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.635.1
Subject(s) - retinal pigment epithelium , gene isoform , drusen , macular degeneration , choroid , bruch's membrane , biology , retina , microbiology and biotechnology , retinal , choroidal neovascularization , eye development , endocrinology , medicine , anatomy , ophthalmology , phenotype , neuroscience , genetics , biochemistry , gene
VEGF in mice is produced as three isoforms, VEGF120, VEGF164 and VEGF188, that differ in their ability to bind heparan sulfate proteoglycan. RPE normally produces only the more soluble isoforms, VEGF120 and VEGF164. We investigated the effect of the absence of soluble VEGF isoforms during early eye development and in the adult. While eye development of mice expressing only VEGF188 (VEGF188/188 mice) appeared normal, TEM analysis revealed age‐dependent defects of the RPE/choroid complex. VEGF188/188 mice displayed changes in the RPE and choroids, characterized by choriocapillaris loss and RPE dysfunction. These degenerative lesions progressed with age with the formation of drusen‐like deposits, RPE apoptosis and choroidal vessel atrophy. These defects were associated with a deficit in visual function evidenced by ERG. The absence of eye defects in embryonic and postnatal VEGF188/188 mice indicate that soluble VEGF isoforms are not required for proper eye development. However, the age‐dependent degenerations observed in VEGF188/188 mice suggest a role for VEGF signaling in the maintenance of the RPE‐choroidal complex. We speculate that in VEGF188/188 mice, Bruch's membrane compromises the diffusion of RPE‐derived VEGF. Reduced VEGF signaling in the choriocapillaris may contribute to the observed abnormalities that recapitulate many of the clinical features of dry AMD.