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Targeting of junctional adhesion molecule-C inhibits experimental choroidal neovascularization.
Invest. Ophthalmol. Vis. Sci. 53, 1584-1591 (2012)
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PURPOSE: To identify the expression of junctional adhesion molecule-C (JAM-C) in choroidal neovascularization (CNV) and evaluate the effect of JAM-C targeting on CNV formation and on cellular functions relevant to CNV in vitro, such as macrophage transmigration, human retinal pigment epithelial (hRPE) cell migration, and monolayer RPE permeability. METHODS: JAM-C expression in CNV was analyzed by real-time PCR, immunoblot analysis, and immunofluorescence staining. CNV area and blood vessel leakage were quantified using isolectin B4 staining and fluorescein angiography, respectively, 1 week after laser treatment. Macrophage infiltration within the CNV area was measured by immunofluorescence, and transmigration through monolayer RPE was analyzed using a transepithelial migration assay. After JAM-C shRNA transfection, human RPE cell migration was quantified using a transwell assay, and monolayer RPE permeability was determined by measuring the apical-to-basolateral movements of sodium fluorescein. RESULTS: JAM-C expression was upregulated during CNV formation after laser treatment in a time-dependent manner. However, no change in JAM-C expression was found in the retina up to 14 days after laser treatment. JAM-C targeting by intravitreal injection of JAM-C Fc chimera inhibited CNV, blood vessel leakage, and macrophage infiltration. JAM-C Fc chimera inhibited basolateral-to-apical transmigration in vitro through a monolayer of hRPE of macrophages from patients with wet AMD. In addition, shRNA-mediated JAM-C knockdown inhibited hRPE cell migration and hRPE permeability. CONCLUSIONS: JAM-C blockade may prove useful for CNV suppression by inhibiting macrophage transmigration, RPE cell migration, and monolayer RPE barrier malfunction.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0146-0404
Quellenangaben Band: 53, Heft: 3, Seiten: 1584-1591
Verlag Association for Research in Vision and Ophthalmology (ARVO)
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)