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Phenotypic Investigation of Cell Junction–Related Proteins in Gelatinous Drop-Like Corneal Dystrophy

¹From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medicine, Kyoto, Japan; the ²Research Center for Regenerative Medicine, Doshisha University, Kyoto, Japan; the ³Department of Ophthalmology, Nantan General Hospital, Kyoto, Japan.

PURPOSE. To identify the molecules involved in the pathogenesis of gelatinous drop-like corneal dystrophy (GDLD) by using immunohistochemical analysis of the expression of tight junction (TJ)-, desmosome-, and basement membrane (BM)–related proteins in human corneas with GDLD.

METHODS. Mutation analysis was performed on samples from three Japanese women with GDLD. Four corneal buttons from these patients were examined histopathologically by Congo red staining and immunohistochemical analysis for the expression of TJ-related proteins (ZO-1, occludin, and claudin-1), desmosome components (desmoplakin), BM-related proteins (integrins 6, ß4, 3, and ß1; laminin-5; and collagens IV and VII), amyloid P component, and lactoferrin.

RESULTS. Mutation analysis revealed that all three women had the Q118X mutation on M1S1. There were accumulations, primarily beneath the epithelium, of Congo-red–positive deposits with birefringence under polarized light. The BM was abnormally thickened and demonstrated a bandlike area. Immunofluorescence analysis revealed that neither ZO-1 nor occludin was expressed in the TJ areas of surface epithelial cells; there was no expression of claudin-1 or desmoplakin in the epithelial surface layer of GDLD corneas. Integrins 6, ß4, 3, and ß1 was expressed along the serrated surface of the BM, laminin-5 and collagens IV and VII were widely expressed throughout the BM, and lactoferrin was expressed in the amyloid deposits and the thickened BM.

CONCLUSIONS. This is the first demonstration of the unique expression patterns of the major cell-junction–related proteins in GDLD corneas. The results show that in corneas with the Q118X mutation, there is a disturbance in cell-to-cell and cell-to-substrate junctions. These findings are an important step toward elucidating the pathogenesis of GDLD.