Differential expression of transcription factors in moderate and severe Fuchs endothelial corneal dystrophy.

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) results in the death of the nonproliferative endothelial cells of the posterior corneal surface, leading to corneal swelling, clouding, and potential blindness. Few studies have suggested the potential role of transcription factors in the endothelial to mesenchymal transition (EnMT) during disease progression. This study aimed to evaluate the expression of selected transcription factors in the corneal endothelium of FECD patients to understand their role in disease pathogenesis.

DESIGN: This is a prospective, pilot, case-control study for studying the gene expression in patients with FECD. Transcription factors ZEB1, TCF4, smad proteins (SMAD3, SMAD4), zinc finger proteins SNAI1 and SNAI2, lymphoid enhancer binding factor 1 (LEF1), N-cadherin (CDH2), claudin 10 (CLDN10), and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2/NRF2), which are involved in the EnMT, were selected for the study. Fourteen FECD endothelia were compared with 15 control endothelia for the gene expression analyses using quantitative real-time PCR.

RESULTS: Significant differential expressions were seen in the levels of SMAD3 (P = 0.0251) in moderate cases compared to control tissues. Further, TCF4 and NFE2L2 showed significantly different expressions among the moderate and severe cases (P = 0.0262 and P = 0.0350, respectively), with expressions decreasing with severity, indicating their possible role in disease progression.

CONCLUSIONS: Our pilot study on transcription factor gene expressions in FECD patients' tissue samples suggests NRF2 and TCF4 to play an important role in the disease pathogenesis and progression.