Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma.

Journal Article (Journal Article)

PURPOSE: To identify the specific genes in human trabecular meshwork (TM) related to POAG. METHODS: Primary open-angle glaucoma TM specimens were obtained from routine trabeculectomy surgery. Nonglaucomatous control TM specimens were dissected from donor eyes using the same approach as a standard trabeculectomy. All cases were screened for myocilin (MYOC) mutations. Total RNA was extracted, labeled, and hybridized to Illumina HumanWG-6 BeadChips. Expression data were normalized and analyzed using the R package limma in Bioconductor. Pathway analyses were performed using DAVID Bioinformatics Resources. RESULTS: Our study included surgical TM specimens from 15 cases and 13 controls. One case was identified with a heterozygous Q368X MYOC mutation. If TMs were available from both eyes in an individual, the expression data were combined for analysis. The following three comparisons were performed for differential analyses: (1) MYOC POAG case versus 14 non-MYOC POAG cases, (2) MYOC POAG case versus 13 controls, and (3) 14 non-MYOC POAG cases versus 13 controls. Limited by one MYOC case in comparisons 1 and 2, expression changes were reported comparing the fold changes but without P values. Comparison 3 identified 483 genes, including 36 components of TM exosomes. Gene ontology analysis identified several enriched functional clusters, including cell adhesion, extracellular matrix, and secretion. CONCLUSIONS: This is the largest TM expression study of POAG cases and controls performed to date and represents the first report of TM expression in a patient having POAG with a Q368X MYOC mutation. Our data suggest the potential role of endocytic and exosome pathways in the pathogenesis of POAG.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Allingham, RR; Qin, X; Layfield, D; Dellinger, AE; Gibson, J; Wheeler, J; Ashley-Koch, AE; Stamer, WD; Hauser, MA

Published Date

  • September 27, 2013

Published In

Volume / Issue

  • 54 / 9

Start / End Page

  • 6382 - 6389

PubMed ID

  • 24003086

Pubmed Central ID

  • PMC3787658

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.13-12128


  • eng

Conference Location

  • United States