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S. Chen, S. S. Chaurasia, A. K. Riau, T. T. L. Wong, E. Tai, J. W. Chew, L. Tong; Global Micro RNA and Messenger RNA Changes in Pterygium. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2403.
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© ARVO (1962-2015); The Authors (2016-present)
Pterygium is a common human ocular surface disease that is characterized by fibrovascular proliferation of the conjunctiva. It is a condition of aberrant wound healing, with an unknown etiology and threatens vision as it invades the cornea. Endogenously produced micro(mi)RNA regulates gene expression in various diseases of wound healing and possibly pterygium. We aimed to investigate the role of miRNA in pterygium.
Paired human pterygium and conjunctival tissues were obtained from patients diagnosed with primary pterygium. Comprehensive profiling of miRNA in pterygium was performed using Exiqon miRCURY LNATM microRNA Array and transcript level changes were evaluated using Affymetrix Human Genome U133A GeneChip. Analysis of results was performed using Agilent GeneSpring GX 10.0 platform. The TargetScan module predicted miRNA target sites within 3’ untranslated regions of mRNAs known to regulate wound healing processes. Statistically significant changes in miRNA level were matched to reciprocal changes in their predicted target transcripts. These changes were validated at the transcript level using fluorescent in-situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR), and at the protein level using immunofluorescent staining.
Analysis of the miRNA array found 6 miRNAs to be significantly elevated and one to be down-regulated in pterygium compared to conjunctival control. We found that hsa-miR-766 was up-regulated (2.57-fold) and hsa-miR-215 down-regulated (0.49-fold) in pterygium compared to conjunctiva. Transcript levels of predicted hsa-miR-766 targets, nuclear receptor subfamily (NR) 4A1 and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1), were down-regulated in pterygium compared to conjunctiva by 0.53 and 0.64 folds respectively. Collagens (COL) 3A1 and 4A2, both targets of hsa-miR-215, were up-regulated in pterygium by 3.01 and 3.11 folds respectively. Changes in the expression levels of miRNAs and their candidate target genes were further confirmed in fluorescent ISH and immunofluorescent staining, and localized to different regions of pterygium epithelia or stroma.
Derangement of hsa-miR-766 and hsa-miR-215 may cause widespread changes in genes that regulate wound healing processes such as matrix rearrangement, cell proliferation and adhesion, resulting in pterygium formation. Targeting miRNA may be a possible therapeutic approach in this disease.
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