Fuchs Endothelial Corneal Dystrophy: Strong Association with rs613872 Not Paralleled by Changes in Corneal Endothelial TCF4 mRNA Level

Abstract

Fuchs endothelial corneal dystrophy (FECD) is a common corneal endotheliopathy with a complex and heterogeneous genetic background. Different variants in the TCF4 gene have been strongly associated with the development of FECD. TCF4 encodes the E2-2 transcription factor but the link between the strong susceptibility locus and disease mechanism remains elusive. Here, we confirm a strong positive association between TCF4 single nucleotide polymorphism rs613872 and FECD in Polish patients (OR = 12.95, 95% CI: 8.63-19.42, χ (2) = 189.5, p < 0.0001). We show that TCF4 expression at the mRNA level in corneal endothelium (n = 63) does not differ significantly between individuals with a particular TCF4 genotype. It is also not altered in FECD patients as compared to control samples. The data suggest that changes in the transcript level containing constitutive TCF4 exon encoding the amino-terminal part of the protein seem not to contribute to disease pathogenesis. However, considering the strong association of TCF4 allelic variants with FECD, genotyping of TCF4 risk alleles may be important in the clinical practice.

Figure 1

Characteristic features of FECD. (a) Slit-lamp photography shows the presence of pathological guttae, focal excrescences of Descemet's membrane at the level of corneal endothelium in a patient with FECD. (b) Confocal microscopy image of the corneal endothelium in a control subject demonstrates a regular mosaic of the endothelial monolayer with bright cell bodies and dark, hexagonal cell boundaries. (c) Confocal microscopy in a patient with FECD reveals pleomorphism and polymegathism of the endothelium and typical guttae as dark bodies with a central bright reflex.

Figure 2

Expression of TCF4 in corneal endothelial cells. The amount of TCF4 mRNA was quantified by real-time PCR in relation to RPL13A. (a) Expression of TCF4 in FECD patients with respect to a different TCF4 genotype at rs613872 (TT n = 3, TG n = 31, and GG n = 6) is shown; ns: nonsignificant. (b) Average values of TCF4 mRNA expression in control samples (white bars) and FECD patients (black bars) are shown; ns: nonsignificant.