Kruppel‐like factor 5 (KLF5) as a genetic factor associated with the etiopathogenesis of Keratoconus

Abstract

Aims: To analyse expression and genotype of Krüppel‐Like Factor 5 (KLF5) gene in the corneal epithelium of eyes with Keratoconus (KC) compared to normal eyes (controls); as well as, to determine the effect of several pro‐inflammatory cytokines on the KLF5 expression by an in vitro study.Methods: 64 corneal epithelium samples from 53 KC and 11 controls were included in this study. KC samples were collected from patients who received crosslinking epi‐off or penetrating keratoplasty for their mild to advanced KC. Control samples were collected from dead donors with healthy corneas. Molecular determinations to measure KLF5 expression and genotype on these samples were performed respectively by qPCR and TaqMan targeting the SNP of interest (rs17285550). In addition, using a cell line of healthy corneal epithelial cells, incubations with increasing concentrations of interleukin 6 (IL6), interleukin 1 beta (IL1β), and tumour necrosis factor alpha (TNFα) were performed to determine the KLF5 response to a pro‐inflammatory environment. KLF5 expression in the stimulated cell cultures was assessed by qPCR analysis.Results: KC samples evidenced significantly higher levels of KLF5 gene expression than the controls (p < 0.0001). The GG genotypes showed an upward tendency for higher expression of KLF5 in the KC group. Higher IL6, IL1β, and TNFα concentrations contribute to a significatively KLF5 overexpression in corneal epithelial cell cultures.Conclusions: Overexpression of KLF5 in the corneal epithelium of KC patients and its upregulation against a proinflammatory microenvironment, could lead to an inadequate epithelial barrier function that destabilizes the surrounding corneal layers and contributes to the KC pathology. KLF5 represents a promising target for gene therapy in KC.