Analysis of molecular mechanisms that predispose patients to develop post-PRK haze
Abstract
Purpose
Factors that predispose certain patients to develop post-surgical haze remain unknown.We analyzed gene expression in corneal epithelium collected from patients prior to haze development following PRK. We further developed an in-vitro model to study haze using TGFβ that mimics pre-disposed and post haze conditions.
Methods
Corneal epithelium was collected intraoperatively from patients undergoing PRK. 4 eyes that developed haze postoperatively and 10 eyes of age matched controls without haze were analysed. Microarray analysis was followed by bioinformatics and validation. In vitro studies were performed on HCE cells on differential doses of TGFβ with or without wound for inflammatory markers, structural & pro-fibrotic genes and regulators of signaling cascades.
Results
Microarray analysis revealed 1100 up regulated and 1700 down regulated genes in haze patients. ECM- Receptor interactions were elevated in patients prior to haze induction while Wnt signaling genes and CXC motif chemokines were reduced. Structural genes (Col I, Col IV, MMP2 & 14, TIMP1) were reduced in haze patients which correlated with in-vitro model. Inflammatory factors TNFα, IL-11 were elevated, but IL6 and IL1 did not show appreciable changes. Regulators of signaling cascades EGFR and Wnt3a were reduced in haze patients & in vitro. We propose a signal transduction network including few novel genes like PREX1, PXDN, SOX17, WNT3A, CXCL10 etc which can be factors that predispose patients to haze.
Conclusions
Our study shows that molecular factors poise the cornea in some patients to developing corneal haze after surgery.
