Expression profiling in glaucomatous human lamina cribrosa cells based on graph-clustering approach

Curr Eye Res. 2013 Jul;38(7):767-73. doi: 10.3109/02713683.2013.770039. Epub 2013 Mar 13.

Abstract

Purpose: In primary open angle glaucoma (POAG) patients, elevated intraocular pressure usually leads to extracellular matrix remodeling and astrocytes activation. Thus, lamina cribrosa (LC) cells may play an important role in POAG progression. The objective of this study was to comprehensively explore gene expression profiles in LC cells of POAG patients.

Materials and methods: Using the GSE13534 microarray datasets downloaded from Gene Expression Omnibus database, the differentially expressed genes (DEGs) between LC cells from POAG patients and controls were firstly screened based on the classical t-test and false discovery rate <0.05 as a significant threshold. Subsequently, these DEGs were grouped into gene sets using a graph-clustering approach. The underlying molecular mechanisms were investigated by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.

Results: A total of 57 DEGs were identified and 478 co-expression relationships were constructed among these DEGs. Among them, cytochrome p450 family 1 subfamily B (CYP1B1), brain-derived neurotrophic factor (BDNF) and myelin basic protein (MBP) showed high-degree relationships and they could interact with several genes. CYP1B1 is an important genetic gene involved in POAG and BDNF is an effective growth neurotrophic factor to weak POAG damage. MBP, versican (VCAN), integrin, alpha 4 (ITGA4) and N-cadherin (CDH2) may be involved in extracellular matrix remodeling in LC cells. FZD2 and FZD7 were enriched in basal cell carcinoma pathway.

Conclusions: The results demonstrate that the genes above may be associated with the pathogenesis of POAG.

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cells, Cultured
  • Cluster Analysis
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / pathology
  • Humans
  • Intraocular Pressure
  • Oligonucleotide Array Sequence Analysis
  • Optic Disk / metabolism*
  • Optic Disk / pathology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Brain-Derived Neurotrophic Factor
  • Cadherins
  • Extracellular Matrix Proteins