Immunohistochemical Expression of Secreted Frizzled-Related Protein-1 (SFRP-1) In Keratoconic Epithelium: A Useful Marker In Keratoconus Pathogenesis Research And Management

Abstract

Purpose: : Keratoconus ia a bilateral corneal ectasia that is diagnosed clinically and is treated with special contact lenses. In severe cases, corneal transplants may be necessary. The physiopathology of this disease is not fully understood. Secretory frizzled-related protein-1 (SFRP-1) has recently been shown to affect apoptosis in wound healing and in some carcinoma models. For example, in prostate cancer, SFRP-1 can affect epithelial/stromal interactions. This protein has been investigated in a small series of keratoconus cases. The aim of this study is to investigate and analyse, through immunohistochemistry (IHC) expression, a potential role of SFRP-1 in keratoconic (KC) corneal epithelium in a large case series.

Methods: : Using a Leitz Laborlux 12 light microscope, corneal epithelium was examined histologically in eighteen (18) KC patients, and ten (10) control corneas obtained from enucleated globes of children diagnosed with retinoblastoma. The control corneas displayed normal architecture and histological features in all corneal layers. IHC was performed using the automated Ventana Benchmark system with a polyclonal SFRP-1 antibody (Abcam).

Results: : Seventeen of 18 KC cases (94.4%) were positive for SFRP-1 immunostaining. SFRP-1 immunostaining was diffuse and intense in 13/18 of KC epithelia (72.2%), mostly in the basal layer. Four (4/18) (22.2%) of the KC epithelia had a non diffuse and a less intense positive immunostaining profile. Only 1/18 (5.6%) of KC cases was negative for SFRP-1. All (10/10) (100%) control corneal specimens were negative for SFRP-1 expression.

Conclusions: : SFRP-1 is expressed by IHC analysis in 17/18 (94.4%) of our KC patients group and was absent in all 10 control corneas. The drastic difference in expression of SFRP-1 in KC cases compared to controls confirms the significant role of SFRP-1 in both the pathogenesis and progression of keratoconus. It also provides further evidence implicating apoptosis of corneal epithelial cells as a significant event in KC corneas. Further investigation of this protein in order to verify whether manipulation of its expression would be useful in management of keratoconus is warranted.

Keywords: keratoconus • cornea: epithelium • immunohistochemistry