September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Global gene expression profiling in meibomian gland dysfunction involving peripheral blood
Author Affiliations & Notes
  • Ling Lee
    Brien Holden Vision Institute, Sydney, New South Wales, Australia
    School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia
  • Qian Garrett
    School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia
  • Subhabrata Chakrabarti
    LV Prasad Eye Institute, Hyderabad, India
  • Judith Flanagan
    Brien Holden Vision Institute, Sydney, New South Wales, Australia
    School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia
  • Eric B Papas
    Brien Holden Vision Institute, Sydney, New South Wales, Australia
    School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Ling Lee, None; Qian Garrett, None; Subhabrata Chakrabarti, None; Judith Flanagan, None; Eric Papas, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4797. doi:
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    • Get Citation

      Ling Lee, Qian Garrett, Subhabrata Chakrabarti, Judith Flanagan, Eric B Papas; Global gene expression profiling in meibomian gland dysfunction involving peripheral blood. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4797.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Meibomian gland dysfunction (MGD) is a complex condition, a significant contributor to evaporative dry eye, and presents with a multifactorial etiology. The underlying molecular mechanisms occurring in MGD have been little explored. This case-control study aims to investigate MGD-associated differential gene expression patterns based on global gene expression profiling of peripheral blood.

Methods : Participants with moderate to severe MGD (n=12) and healthy age-, gender- and ethnicity-matched controls (n=12) were recruited from a Southern Indian population at the L. V. Prasad Eye Institute, Hyderabad, India. RNA was extracted from peripheral blood using the TempusTM spin column kit and treated with GLOBINClearTM for excess globin removal. Gene expression profiling was carried out using lllumina Human HT-12 v4 microarray BeadChips and raw data were acquired through GenomeStudio software. Data pre-processing, normalization and differential expression were performed using the R-Bioconductor software. Pathway and network analyses were performed using MetacoreTM software where thresholds were set at p<0.05 and fold-change >1.2 to explore potential biological pathways and transcription factors associated with MGD.

Results : Of the 25,390 transcripts analyzed, there were no genes differentially expressed between the cases and controls (all FDR-adjusted p>0.10). Pathway analyses revealed the biological processes associated with MGD included platelet aggregation, which may be associated with an inflammatory component in MGD, B-Raf signaling, inflammation - histamine signaling and cytoskeleton remodeling (all pathways FDR-adjusted p<0.001). Network analyses revealed key transcription factors CREB1, AR and ESR1 (all p<0.001), which are involved in hormonal regulation, supporting these as potential candidates in MGD pathogenesis.

Conclusions : Global gene expression analysis did not reveal any major candidate genes suggesting gene expression differences associated with MGD in peripheral blood are mild and difficult to detect. However, biological pathways identified in this study as being associated with MGD provide an alternative insight into MGD pathogenesis. Functional validation of the genes within these pathways and their cellular interactions could provide further clues to MGD disease processes along with their roles as potential biomarkers.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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