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Kameran Lashkari, Jie Ma, Gianna Teague, Jorge Arroyo; Expression of VEGF-C, VEGF-D and their Cognate Receptors in Experimental Choroidal Neovascularization and Clinical AMD. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4999.
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VEGF-C has been implicated in tumor-associated and corneal angiogenesis through its effects on lymphangiogenesis and activation of VEGFR3. However, recent evidence implicates VEGF-C and D in pathological angiogenesis in absence of lymphatic involvement, possibly through activation of VEGFR2. The goal of this study is to define the role of VEGF-C and its cognate receptors in retinal angiogenesis including neovascular AMD and related disorder.
The levels of VEGF-C and D, and soluble VEGF receptors, R1, R2 and R3 were measured in vitreous samples of subjects with various vitreoretinal conditions using combination of Luminex and Elisa assays. The mouse model of laser-induced choroidal neovascularization (CNV) was used to detect the expression of VEGF-C, D and receptors, R2 and R3 using imaging and immunohistochemistry. Expression of these factors was also examined in donor eyes with various stages of AMD.
Both VEGF-C and D and soluble (s) R1, R2 and R3 were detectable in the human vitreous. sR3 levels averaged 200 pg/ml in control subjects, and one log order higher than sR2 levels. The respective concentrations of VEGF-C and D positively correlated with age and were affected by retinal diseases including AMD. VEGF-C and its cognate receptors were detected within cellular components of laser-induced CNV membranes. A similar expression pattern was seen in clinical specimens of AMD.
Based on these examinations, VEGF-C, D and sVEGFRs are detectable in the human vitreous, positively associated with age, and affected by disease states such as AMD. VEGF-C and D were detected within experimental and clinical CNV membranes. VEGF-C and D may participate in pathological angiogenic processes such as neovascular AMD in absence of any observed lymphangiogenesis.
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