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• W2314644927 abstract "Purpose.: Corneal neovascularization can cause loss of vision. The introduction of anti-VEGF therapy has been a major improvement in therapeutic options. Recently, we established Kelch-like Ect2-interacting protein (KLEIP/KLHL20) knockout mice as a model of spontaneous corneal neovascular dystrophy. The aim of the present study was to characterize corneal neovascularization in progressive corneal dystrophy in KLEIP−/− mice, to evaluate the efficacy of anti-VEGF therapy, and to identify novel molecular regulators in this experimental model. Methods.: Corneal neovascularization was assessed by immunohistochemistry. Vascular endothelial growth factor signaling was inhibited by injection of a blocking antibody. Microarrays were used to measure expression of mRNA and microRNA (miRNA) in dystrophic corneae. Results were validated by immunohistochemistry and Western blotting. Results.: Blood vessels and lymphatics grew from the limbus toward the dystrophic epithelium in corneae of KLEIP−/− mice. Blocking VEGF signaling did not reduce phenotype progression. Correspondingly, microarray analysis revealed no upregulation of canonical vascular growth factors in late dystrophy. During phenotype progression, angiopoietin-1 expression increased while miR-204 expression decreased. Bioinformatic analysis identified a binding site for miR-204 in the angiopoietin-1 gene. Validation by in vitro experiments confirmed regulation of angiopoietin-1 by miR-204. Conclusions.: Vascular endothelial growth factor does not act as a major player in corneal neovascularization in KLEIP−/− mice. However, the proangiogenic factor angiopoietin-1 was strongly upregulated in late-stage phenotype, correlating with loss of miR-204 expression. Correspondingly, we identified miR-204 as a novel regulator of angiopoietin-1 in vitro. These findings may explain the incomplete efficacy of anti-VEGF therapy in the clinic and may provide new candidates for pharmaceutical intervention." @default.
• W2314644927 created "2016-06-24" @default.
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• W2314644927 date "2014-07-14" @default.
• W2314644927 modified "2023-10-12" @default.
• W2314644927 title "Angiopoietin-1 Is Regulated by miR-204 and Contributes to Corneal Neovascularization in KLEIP-Deficient Mice" @default.
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• W2314644927 doi "https://doi.org/10.1167/iovs.13-13619" @default.
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• W2314644927 hasPublicationYear "2014" @default.
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