title: Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Human Genetics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Liu
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.forename: Xuejun
authors.initials: X
authors.lastname: Qin
authors.forename: David
authors.initials: D
authors.lastname: Layfield
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Dellinger
authors.forename: Jason
authors.initials: J
authors.lastname: Gibson
authors.forename: Joshua
authors.initials: J
authors.lastname: Wheeler
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.forename: W Daniel
authors.initials: WD
authors.lastname: Stamer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009154:Mutation; D012313:RNA / Q000235:genetics*; D014129:Trabecular Meshwork / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D012313:RNA; D000099179:Myocilin
keywords: PAX6; exosome; gene expression; myocilin; trabecular meshwork