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S. Liu, S. M. Richards, D. A. Sullivan; Changes in Gene Expression in Meibomian Gland Dysfunction. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3401.
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© ARVO (1962-2015); The Authors (2016-present)
Meibomian gland dysfunction (MGD) is believed to be the leading cause of dry eye syndrome throughout the world. However, the precise mechanism(s) underlying the pathogenesis of this disease are unclear. In this study we sought to identify meibomian gland genes that may promote the development and/or progression of human MGD.
Lid tissues were obtained from male and female MGD patients and age-matched controls (n = 6/group) after eyelid surgeries. Meibomian glands were isolated and then processed for RNA extraction and the analysis of gene expression by using Illumina humanHT-12 v3 expression beadchips. These chips target more than 25,000 annotated genes and contain over 48,000 probes. Standardized data were generated with Illumina BeadStudio software, background subtraction and cubic spline normalization, and analyzed with GeneSifter.Net bioinformatics and statistical software.
Our results show that MGD is associated with significant (p < 0.05) alterations in the expression of almost 400 genes in the human meibomian gland. The levels of 197 transcripts, including small proline-rich proteins 3, 2A and 2F, cystatin A, keratins 10, 6B and 6C, and S100 calcium binding proteins A7, A8 and A9, were significantly increased, while the expression of 194 genes, such as for alpha polypeptide platelet-derived growth factor receptor, was significantly decreased. These changes were accompanied by alterations in many gene ontologies, including an elevation of biological processes for keratinocyte differentiation and ectoderm development, and a suppression of others like cell growth. In addition, MGD was associated with a significant rise in pathways linked to deoxyribonuclease and structural molecule activities and cornified envelope components, and a reduction in those related to cytoplasmic vesicles.
Our findings demonstrate that MGD is accompanied by multiple changes in gene expression in the meibomian gland. The nature of these alterations, including the upregulation of genes encoding small proline-rich proteins and S100 calcium binding proteins, suggest that keratinization and inflammation may play important roles in the pathogenesis of MGD.
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