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A. K. Riau, T. T. Wong, S. S. Chaurasia, S. N. Finger, L. Tong; Pterygium is Associated With Differential Dna Methylation of Promoters of Matrix Remodeling and Cell Adhesion Related Genes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2406.
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© ARVO (1962-2015); The Authors (2016-present)
Pterygium is a common ocular surface disease characterized by abnormal epithelial and fibrovascular proliferation, invasion, and matrix remodeling. This lesion, which advances to the center of the cornea, impairs vision and causes irritation. The pathogenesis of pterygium remains unclear, and current treatment is solely surgical excision. We aim to investigate the DNA methylation status of the promoters of matrix remodeling and cell adhesion related genes in pterygium.
Genomic DNA was extracted from pterygium and uninvolved conjunctival tissue from the patients who underwent surgery. The EpiTYPER Sequenom technology, based on differential base cleavage and bisulfite sequencing was used to evaluate the extent of DNA methylation of a panel of matrix remodeling and cell adhesion related genes. Changes in transcript level were examined in an Affymetrix GeneChip study previously performed. Biologically relevant DNA methylation was defined as those consistent with a reduced or increased transcript and protein level.
In pterygium, three CpG units at +85, +91 and +95 bp downstream of TGM-2 transcription initiation site were significantly hypermethylated (p<0.05), whereas hypomethylation was detected at CpGs +739 bp downstream of MMP-2 transcription start site, and -322, -531, -779 and -785 bp upstream of the CD24 transcription start site. RT-qPCR, western blot and immunofluorescent staining showed that transcript and protein expression were reduced for TGM-2 and increased for MMP-2 and CD24. Inhibition of methylation in cultured conjunctival epithelial cells increased these transcripts.
We found regions of aberrant DNA methylation which were consistent with changes in TGM-2, MMP-2, and CD24 transcript and protein expression. Since these genes are related to cell adhesion and matrix remodeling, dysregulation may lead to fibroblastic and neovascular changes, and pterygium formation. Clinically, these results may have implications for the prognostication of pterygium, for example detection of epigenetic changes may be important in predicting post surgical recurrence of aggressive lesions.
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