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

Purpose: To investigate the expression of Wnt signalling pathway genes in keratoconic (KC) epithelium.

Methods: RNA was extracted from the epithelium of four KC patients undergoing corneal transplantation and five age-matched controls. The expression of 84 genes known to be involved in the Wnt signalling pathway was tested by reverse transcription-polymerase chain reaction (RT-PCR) with a pathway-targeted array (Human Wnt RT(2) Profiler PCR Array, Superarray).

Results: Using RT-PCR arrays, LEF1, PITX2 and secreted frizzled-related protein 1 (SFRP1) were upregulated more than twofold in KC compared with control epithelium. Only SFRP1 was significantly upregulated, approximately 25-fold compared with pooled controls (range 9.12-fold to 98.6-fold; P = 0.019). SFRP1 expression was associated with patient age and possibly the rate of progression of the keratoconus. Immunohistochemistry was used to assess SFRP1 protein distribution and confirm the SFRP1 microarray result (n = 3 KC and n = 2 control corneas). SFRP1 immunolablelling was seen in all KC corneas, mostly in the basal epithelium; however, control corneas showed minimal SFRP1 immunoreactivity.

Conclusion: 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.