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Purpose  Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive corneal dystrophy that causes severe vision loss. Because of its poor prognosis, there is a demand for novel treatments for GDLD. Here, we establish a new in vitro disease model of GDLD based on immortalized human corneal epithelial (HCE-T) cells.    Methods  By using transcription activator-like effector nuclease plasmids, tumor-associated calcium signal transducer 2 ( TACSTD2 ) and its paralogous gene, epithelial cell adhesion molecule ( EpCAM ), were knocked out in HCE-T cells. Fluorescence-activated cell sorting was performed to obtain cells in which both  TACSTD2  and  EpCAM  were knocked out (DKO cells). In DKO cells, the expression levels and subcellular localizations of claudin (CLDN) 1, 4, and 7, and ZO-1 were investigated, along with epithelial barrier function. By using DKO cells, the feasibility of gene therapy for GDLD was also investigated.    Results  DKO cells exhibited decreased expression and aberrant subcellular localization of CLDN1 and CLDN7 proteins, as well as decreased epithelial barrier function. Transduction of the  TACSTD2  gene into DKO cells nearly normalized expression levels and subcellular localization of CLDN1 and CLDN7 proteins, while significantly increasing epithelial barrier function.    Conclusions  We established an in vitro disease model of GDLD by knocking out  TACSTD2  and its paralogous gene,  EpCAM,  in HCE-T cells. This cell line accurately reflected pathological aspects of GDLD.    Translational Relevance  We expect that the cell line will be useful to elucidate the pathogenesis of GDLD and develop novel treatments for GDLD.

A New in Vitro Model of GDLD by Knocking OutTACSTD2and Its Paralogous GeneEpCAMin Human Corneal Epithelial Cells