Secreted frizzled‐related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment

Abstract

SFRP1 is highly upregulated in the epithelium of these KC patients, suggesting a role in the pathogenesis and progression of keratoconus. Future investigations are required to establish if SFRP1 may be a potential marker of KC progression or if manipulation of its expression can be used to therapeutic effect in this disease.

Increased Expression of Secreted Frizzled-Related Protein-1 and Microtubule-Associated Protein Light Chain 3 in Keratoconus

“…An earlier study concluded that SFRP-1 is highly upregulated in the corneal epithelium of keratoconus patients based on immunohistochemical findings. 17 The results of our study are comparable with the findings reported therein. Although our study did not investigate the expression of Wnt signaling pathway genes, the earlier study indicates that SFRP-1 was upregulated more than 2-fold in keratoconus compared with control epithelium using RT-PCR arrays.…”

“…[13][14][15][16] A recent investigation of the expression of Wnt signaling pathway genes in keratoconic epithelium has been reported. 17 In this study, the secreted frizzled-related protein-1 (SFRP-1) was reported to be upregulated by 25-fold in the corneal epithelium of patients with keratoconus. 17 Based on this background, it is hypothesized that dysregulation of Wnt signaling through aberrant up-or downregulation of SFRP-1 may contribute to the pathogenesis of keratoconus.…”

Study of <b><i>VSX1</i></b> Mutations in Patients with Keratoconus in Southwest Iran Using PCR-Single-Strand Conformation Polymorphism/Heteroduplex Analysis and Sequencing Method

“…Although the pathogenic role of VSX1 is now accepted by many authors, only a small number of patients show mutations in this gene. In addition, several loci for the disease have been mapped [10,16,22,41], and a large number of genes have been shown to be up- or downregulated in KC corneal tissues [42,43,44]. Reports have confirmed the genetic heterogeneity of the disease and also support the hypothesis that in some pedigrees the defect could be inherited as a multifactorial trait.…”

Proteomic and gene expression patterns of keratoconus

“…[457] The deregulation of cytokeratins and immunoglobulins associated with the disease need to be investigated mechanistically in the light of the degradation process associated with ectasia and tissue remodeling. However, the association with raised oxidative status of the KC cornea evidenced by LOX deregulation[20] and upregulation of the Wnt pathway[2122] is very interesting since they may prove to be novel intervention nodes for disease management. Furthermore, increased expression of molecules such as S100A4 and alpha enolase, an epithelial cell metabolite, which are associated with inflammation, may have important roles in KC pathogenesis.…”

“…This is particularly interesting because a more recent study specifically on the Wnt signaling pathway demonstrates that Secreted frizzled-related protein 1 (SFRP1) protein is highly expressed in KC epithelia at both the RNA and protein levels compared to normal. [22] Apart from this, recent literature suggests that inflammatory molecules and abnormal levels of enzymes are present in subjects with KC. [3623] Lema et al ., have demonstrated that tears from KC patients have higher levels of interleukin 6 (IL6), tumor necrosis factor alpha (TNF-α), and MMP9 compared to healthy controls.…”