Differential molecular signature of ectatic and non-ectatic areas from Keratoconus patient corneas

Purpose

To evaluate if the gene expression profile of corneal epithelium from the cone area in Keratoconus (KC) differs from the peripheral non-ectatic areas.

Hypothesis: The ectasia in Keratoconic cornea is localized to the cone while the peripheral areas are apparently normal. Hence we hypothesized that within the cone of a KC patient cornea, the structural weakness may be a function of localized gene expression differences

Methods

Study group contained 54 KC patients undergoing epithelium off corneal collagen crosslinking (CXL) and 9 non-ectatic subjects undergoing photo refractive keratectomy (PRK) as controls. The cone vs periphery distinction is based on keratometry and location of the cone based on elevation map. Using a 4.5 mm trephine centered on the cone, epithelium was scraped separately for cone and rest as periphery. In non-ectatic controls, the central 4.5 mm area was taken as cone. Gene expression profiling was performed for each pair of cone and periphery samples by quantitative PCR.

Results

Lysyl oxidase levels were significantly reduced in the cone of KC patients (p = 0.002). Structure related genes COL1 (p = 0.01) and COL4 (p = 0.008) were also reduced significantly in KC patient cones. The cytokines IL6, TGFβ and TNFα did show an increased trend; regulatory cytokine IL10 did not show significant trend. Matrix remodeler MMP9 showed an increasing trend at the cone while its inhibitor TIMP1 showed a reducing trend that was not significant(p = 0.09).

Conclusions

Ectasia in KC may be driven by local molecular factors at the cone that possibly spreads to other parts of cornea as disease progresses.