Pathway abnormality, gene expression may lead to new treatments for keratoconus

NUSA DUA, Indonesia — Abnormalities in the Wnt pathway due to increased expression of secreted frizzled related proteins may allow for better screening of patients and even manipulation of genes to modulate keratoconus, a presenter said here.

Gerard Sutton

"The Wnt pathway did show abnormal expression in keratoconus, and this is a new finding. The sFRP1 was highly upregulated," Gerard Sutton, FRANZCO, FRACS, MBBS, said during the joint meeting of the Asia-Pacific Academy of Ophthalmology and the American Academy of Ophthalmology. "If we can confirm that sFRP1 (secreted frizzled related proteins) is in fact a biomarker for keratoconus progression, that may give us some idea of which patients are going to benefit from corneal cross-linking. ... It may well be a biomarker for those [LASIK] patients who are at risk of developing kerectasia, and maybe sFRP or one of the Wnt related genes could be used to modulate keratoconus."

The Wnt signaling pathway describes a signaling pathway composed of a complex network of proteins involved in controlling many adjustments in the cell nucleus including apoptosis while sFRP acts as a blocker or modulator of the Wnt protein, preventing the Wnt from binding to receptors.

"There are many studies that confirm that, showing that apoptosis may be one of the key mechanisms in keratoconus," Prof. Sutton said. "As it turns out, sFRP has actually been implicated in apoptosis in many other disease states in tissues in the body and, most specifically, in dental and dermal wound healing. Not only that, there has been some manipulation of the sFRP successfully to control wound healing in these tissues."

Researchers in this study were trying to determine if an abnormality in the Wnt pathway is implicated in the pathogenesis of keratoconus. They looked at the corneal epithelium in four keratoconus patients, extracting their RNA for examination. Researchers found that among the 86 genes of the Wnt pathway, sFRP1 was upregulated by 25 times, significantly more than any other gene expression and significantly more than the controls.

"This hadn't been shown in keratoconus before, so we were quite excited by that," he said. "You'll be hearing a lot about [the Wnt pathway] in the years to come."