Proteomics of vitreous humor of patients with exudative age-related macular degeneration

PLoS One. 2014 May 14;9(5):e96895. doi: 10.1371/journal.pone.0096895. eCollection 2014.

Abstract

Background: There is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).

Methods and findings: Eighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.

Conclusions: Proteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Biomarkers / metabolism
  • Case-Control Studies
  • Female
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Gene Expression Regulation
  • Humans
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism
  • Lipocalins / genetics
  • Lipocalins / metabolism
  • Male
  • Middle Aged
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Proteomics*
  • Steroids / therapeutic use
  • Vitrectomy
  • Vitreous Body / chemistry*
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / genetics*
  • Wet Macular Degeneration / metabolism
  • Wet Macular Degeneration / therapy
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Lipocalins
  • Peptide Fragments
  • Steroids
  • alpha 1-Antitrypsin
  • fibrinogen alphaC
  • Bevacizumab
  • Fibrinogen
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase

Grant support

The study was financed in part by the Adolf Messer Stiftung in Königstein, Hessen, Germany; No additional external funding was received for this study. http://www.adolf-messer-stiftung.de/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.