September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Vitreous Proteins Implicated in Idiopathic Macular Hole Formation
Author Affiliations & Notes
  • Sharon D Solomon
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Richard Semba
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Pingbo Zhang
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Randi Turner
    University of Maryland, Baltimore, Maryland, United States
  • Jiang Qian
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Yuming Zhao
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Peter A Campochiaro
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Ingrid E Zimmer-Galler
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Ian Han
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Yannis Mantas Paulus
    Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Syed Mahmood Ali Shah
    Wilmer Eye Institute Johns Hopkins, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Sharon Solomon, None; Richard Semba, None; Pingbo Zhang, None; Randi Turner, None; Jiang Qian, None; Yuming Zhao, None; Peter Campochiaro, None; Ingrid Zimmer-Galler, None; Ian Han, None; Yannis Paulus, None; Syed Mahmood Shah, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4086. doi:
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    • Get Citation

      Sharon D Solomon, Richard Semba, Pingbo Zhang, Randi Turner, Jiang Qian, Yuming Zhao, Peter A Campochiaro, Ingrid E Zimmer-Galler, Ian Han, Yannis Mantas Paulus, Syed Mahmood Ali Shah; Vitreous Proteins Implicated in Idiopathic Macular Hole Formation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4086.

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

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Abstract

Purpose : Idiopathic macular holes (IMH), full-thickness defects of retinal tissue that cause severe vision loss due to disruption of the anatomic fovea, are most common in the sixth through eighth decades of life and are about three times more likely to affect women than men. Despite recent studies using optical coherence tomography (OCT) that have shown abnormal vitreous traction is involved in the formation of macular holes, little is known about the underlying molecular abnormalities that cause the vitreous to pull pathologically on the internal limiting membrane of the retina. We hypothesize that IMH’s are associated with abnormally expressed proteins in the vitreous and will be verified by multiple reaction monitoring (MRM) and immunoblotting. These abnormally expressed proteins may provide novel insight into biological pathways and potential therapeutic targets in patients with IMH’s.

Methods : We conducted a discovery phase investigation involving 40 cases with idiopathic macular hole and 40 age- and sex-matched controls without idiopathic macular hole using mass spectrometry-based label-free quantitative proteomics. We performed the lowess normalization and used DEGSEQ to identify differentially expressed proteins. We also used DAVID to identify the enriched pathways involved in the disease process.

Results : We identified twenty candidate proteins that had >2-fold increased expression in cases compared with controls. There were no proteins that had >2-fold decreased expression in cases compared with controls. The candidate proteins include alpha-2-macroglobulin, which has been implicated in retinal glial cell proliferation, and monocyte differentiation antigen CD14, which can activate inflammatory signaling. Fibrinogen alpha, beta, and gamma chains were also upregulated in the vitreous of subjects with macular hole compared with controls. The Eye Disease Case-Control Study previously described an association of idiopathic macular holes with elevated plasma fibrinogen. Our study extends this finding with an association of elevated vitreous fibrinogen with idiopathic macular holes.

Conclusions : The basic pathophysiology of idiopathic macular holes is poorly understood. Identification of the molecular abnormalities of the vitreous that predispose to idiopathic macular hole formation would lay the groundwork for the development of targeted therapies that could preclude macular hole formation at the earliest stages.

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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