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

Yutao Liu, R. Rand Allingham, Xuejun Qin, David Layfield, Andrew E. Dellinger, Jason Gibson, Joshua Wheeler, Allison E. Ashley-Koch, W. Daniel Stamer, Michael A. Hauser

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6382-6389
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number9
DOIs
StatePublished - Oct 4 2013
Externally publishedYes

Fingerprint

Trabecular Meshwork
Transcriptome
Exosomes
Trabeculectomy
Mutation
Gene Ontology
Primary Open Angle Glaucoma
Computational Biology
Cell Adhesion
Genes
Extracellular Matrix
trabecular meshwork-induced glucocorticoid response protein
Case-Control Studies
Tissue Donors
RNA

Keywords

  • Exosome
  • Gene expression
  • Myocilin
  • PAX6
  • Trabecular meshwork

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma. / Liu, Yutao; Allingham, R. Rand; Qin, Xuejun; Layfield, David; Dellinger, Andrew E.; Gibson, Jason; Wheeler, Joshua; Ashley-Koch, Allison E.; Stamer, W. Daniel; Hauser, Michael A.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 9, 04.10.2013, p. 6382-6389.

Research output: Contribution to journalArticle

Liu, Y, Allingham, RR, Qin, X, Layfield, D, Dellinger, AE, Gibson, J, Wheeler, J, Ashley-Koch, AE, Stamer, WD & Hauser, MA 2013, 'Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma', Investigative Ophthalmology and Visual Science, vol. 54, no. 9, pp. 6382-6389. https://doi.org/10.1167/iovs.13-12128
Liu, Yutao ; Allingham, R. Rand ; Qin, Xuejun ; Layfield, David ; Dellinger, Andrew E. ; Gibson, Jason ; Wheeler, Joshua ; Ashley-Koch, Allison E. ; Stamer, W. Daniel ; Hauser, Michael A. / Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 9. pp. 6382-6389.
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abstract = "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.",
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AU - Liu, Yutao

AU - Allingham, R. Rand

AU - Qin, Xuejun

AU - Layfield, David

AU - Dellinger, Andrew E.

AU - Gibson, Jason

AU - Wheeler, Joshua

AU - Ashley-Koch, Allison E.

AU - Stamer, W. Daniel

AU - Hauser, Michael A.

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N2 - 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.

AB - 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.

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