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Analysis of molecular mechanisms that predispose patients to develop post‐ PRK haze
Author(s) -
Rajiv Kumar N.,
Ghosh A.,
Shetty R.,
Pahuja N.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.1543
Subject(s) - haze , wnt signaling pathway , in vitro , cornea , medicine , corneal epithelium , microarray analysis techniques , ophthalmology , signal transduction , microbiology and biotechnology , biology , gene , gene expression , chemistry , genetics , organic chemistry
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 TGF β 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 TGF β 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 , MMP 2 and 14, TIMP 1) were reduced in haze patients which correlated with in‐vitro model. Inflammatory factors TNF α, IL ‐11 were elevated, but IL 6 and IL 1 did not show appreciable changes. Regulators of signaling cascades EGFR and Wnt3a were reduced in haze patients and in vitro . We propose a signal transduction network including few novel genes like PREX 1, PXDN , SOX 17, WNT 3A, CXCL 10 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.