Literature DB >> 16723450

Antibody blockade of junctional adhesion molecule-A in rabbit corneal endothelial tight junctions produces corneal swelling.

Kenneth J Mandell1, Glenn P Holley, Charles A Parkos, Henry F Edelhauser.   

Abstract

PURPOSE: The ultrastructure of tight junctions in the corneal endothelium has been studied extensively, yet little is known about their molecular composition. Junctional adhesion molecule-A (JAM-A) is a tight junction-associated adhesion protein previously implicated in tight junction assembly and regulation of barrier function. In this study, we sought to investigate the expression and function of JAM-A in the corneal endothelium.
METHODS: Immunofluorescence confocal microscopy was used to investigate expression of JAM-A and the related proteins JAM-C, CAR, and AF-6 in the rabbit corneal endothelium. Corneal endothelial perfusion specular microscopy was then used to test the effects of antibodies to JAM-A on corneal swelling.
RESULTS: The expression of JAM-A was observed in the tight junctions of rabbit corneal endothelium in a localization pattern identical with that of ZO-1, a known marker of the tight junction and binding partner of JAM-A. Expression of related proteins JAM-C and CAR (Coxsackie and adenovirus receptor) was also observed in the corneal endothelium, but their distribution was diffuse and not limited to the tight junction. Expression of AF-6, a known binding partner of JAM-A, was also observed in the tight junction in a pattern similar to ZO-1. Last, functional experiments were performed in which a monoclonal antibody to JAM-A was shown to increase rabbit corneal swelling by 63% compared with the control.
CONCLUSIONS: The results provide new evidence that JAM-A and its binding partner AF-6 are expressed in tight junctions of the corneal endothelium and that JAM-A has a major role in maintaining the corneal endothelial barrier function.

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Year:  2006        PMID: 16723450     DOI: 10.1167/iovs.05-0745

Source DB:  PubMed          Journal:  Invest Ophthalmol Vis Sci        ISSN: 0146-0404            Impact factor:   4.799


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