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M. Saint-Geniez, T. Kurihara, E. Sekiyama, A. Maldonado, P. A. D'Amore; Soluble Vegf Isoforms Are Required for the Maintenance of the Retinal Pigment Epithelium (RPE)-choriocapillaris Complex in the Adult. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1537.
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VEGF in mice is produced from a single gene as three alternatively spliced isoforms, VEGF120, VEGF164 and VEGF188, that differ in their ability to bind heparan sulfate proteoglycan. RPE normally produces VEGF120 and VEGF164, the more soluble isoforms, but virtually no VEGF188. Here we investigated the effect of the absence of soluble VEGF isoforms during early eye development and in the adult.
C57/B6 mice expressing only VEGF188 (VEGF188/188) were generated by knock-in technology and have been previously described. Morphological changes in the eyes of VEGF188/188 mice were evaluated by histology, transmission electron microscopy (TEM) and funduscopy. Alterations in the organization and differentiation of the RPE and choroidal vessels were characterized using sections and flat-mounted choroids by immunostaining for tight junction proteins (ZO-1, beta-catenin), BS1-isolectin and RPE65. ERG recording was used to assess visual function.
While eye development of VEGF188/188 mice appeared normal, TEM analysis revealed age-dependent alterations of the RPE/choroids complex. VEGF188/188 mice displayed abnormalities in the RPE and choroids, beginning around seven months, characterized by loss of the choriocapillaris, defects in the RPE and a marked disruption of the Bruch’s membrane. Changes in the RPE layer mice included cell engulfment, vacuolization, detachment and lipofuscin accumulation. These degenerative lesions progressed with age with the formation of drusen-like deposits, loss of epithelial tight junctions, RPE apoptosis and choroidal vessel atrophy and were associated with a deficit in visual function as evidenced by a reduction of ERG a- and b-waves.
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