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Caren K. Sheng, Xiaoying Zhu, Josh Wallman; VEGF Thins the Choroid Transiently and Increases Scleral GAG Synthesis In Vitro. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3435.
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© ARVO (1962-2015); The Authors (2016-present)
Vascular endothelial growth factor (VEGF) causes vascularization of the retina and choroids in mammals, among other effects (Ferrara 2009). Because insulin or IGF-1 can induce VEGF mRNA expression in the RPE (Lu et al. 1999; Weng et al. 2009), and we have found that insulin causes the RPE to produce unidentified molecules that thin the choroids in vitro (Sheng at al., ARVO abstract 2008, 2009), VEGF may be one of the signals that cause choroidal thinning. We studied whether VEGF165 (V165), a major isoform of VEGF, can affect choroidal thickness and scleral GAG synthesis in vitro.
Eyes from 1-week-old chicks were hemisected and the retinas removed to make eye-cups with either RPE/choroid/sclera (RCS eye-cups), choroid/sclera (CS eye-cups) or just sclera (S eye-cups) in pairs from individual birds. One eye-cup of each pair was incubated with V165 (1,10 or 100ng/mL) in L-15 medium, and the fellow eye-cup was incubated in L-15 alone. Choroidal thickness was measured before and after 1, 2, and 20 hours of incubation. Scleral GAG synthesis was measured after 20 hours or 44 hours of incubation.
In CS, but not RCS, eye-cups, one hour of incubation with V165 significantly reduced the natural choroidal expansion seen in vitro (i.e., caused choroids to be thinner than those of control eyes) at 10 and 100ng/mL (ΔX-ΔN [mean±SEM]: -43±18μm and -44±18μm, respectively), but not at 1ng/mL (-17±26μm). This thinning effect was not sustained after 2 and 20 hours of incubation. The effect of V165 on CS and RCS eye-cups was not significantly different (two-way ANOVA). Furthermore, after 44 hours (but not after 20 hours), V165 significantly increased scleral GAG synthesis 1.4-fold in CS eye-cups at 100ng/mL but not in RCS eye-cups or S eye-cups at any concentration.
The direct transient thinning effect of VEGF on the choroid suggests that VEGF may be one of the signals produced and released by the RPE in the presence of insulin to initiate choroidal thinning.
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