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Wanwen Lan, Tina T. Wong, Louis Tong; Microarray Analysis in Pterygium and in Chronically Medicated Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4024.
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© ARVO (1962-2015); The Authors (2016-present)
Pterygium is a relatively common ocular surface disease characterized by fibrovascular proliferation. Recently, there has been some research indicating that epigenetic changes play a role in the pathology of this condition. We performed global profiling of micro(mi)RNAs in pterygium, compared to un-involved conjunctiva. Glaucoma patients who had chronic medications tend to have pro-inflammatory and pro-scarring type conjunctiva. As an additional control, we compared the levels of miRNAs in the conjunctiva from these patients.
Pterygium tissue (PT) was collected from 3 patients, and paired un-involved conjunctiva (CC) was also obtained. During glaucoma surgery, 3 conjunctiva samples were also obtained from patients who had chronic instillation of glaucoma eyedrops (CG). Microarray analysis for miRNA was performed using the mercury LNA miRNA Array v11.0 kit (Exiqon, Vedbaek, Denmark). This contains capture probes complementary to 385 mature miRNAs registered in miRBase and 43 control capture probes.
From each spot and each channel the median signal intensity is taken and normalized (i.e. background corrected + global lowess). Eleven miRNA were significantly dysregulated in PT compared to CC. In PT, upregulated miRNAs include hsa-miR-766, hsa-miR-625, hsa-miR-549, and hsa-miR-518b, and down-regulated miRNAs include hsa-miR-138, hsa-miR-25, hsa-miR-215 and hsa-miR-26a. Other miRNAs hsa-miRPlus-E1258, hsa-miR-1238 and hsa-miR-623 were also upregulated in PT. Hsa-miR-138 was upregulated by 3.0 fold compared to CC, the most upregulated miRNA in pterygium, followed by hsa-miR-518b (upregulated by 1.75 fold), the second highest significantly upregulated miRNA.Eleven miRNA were significantly dysregulated in CG compared to CC. Hsa-miR-138 was also significantly upregulated (5.7 fold) in CG compared to CC. Other miRNAs upregulated in CG compared to CC were hsa-miRPlus-E1290, hsa-miR-874, hsa-miR-205, miRPlus-A1015, hsa-miR-184, miRPlus-E1066, hsa-miR-1201, hsa-miR-204, miRPlus-E1186 and miRPlus-E1225. Hsa-miR-184 was upregulated 3.6 fold compared to CC.
Unique miRNAs were dysregulated in pterygium, and this may affect target genes involved in matrix regulation and angiogenesis. Since all but one of the dysregulated genes in chronically medicated conjunctiva were distinct from these miRNAs, we conclude that the pathology in pterygium is regulated differently at the level of miRNA from other inflammatory/pro-fibrotic conditions of the conjunctiva. This study has implications for modulation of miRNAs in pterygium as well as in chronic glaucoma patients.
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