Distinctive and pervasive alterations in aqueous humor protein composition following different types of glaucoma surgery

Mol Vis. 2015 Aug 25:21:911-8. eCollection 2015.

Abstract

Purpose: To investigate whether specific glaucoma surgeries are associated with differences in aqueous humor protein concentrations compared to eyes without filters.

Methods: In this cross-sectional study, aqueous humor samples were prospectively collected from control subjects who underwent routine cataract surgery (n=14) and from patients who had different glaucoma filters: Baerveldt aqueous shunt (n=6), Ahmed aqueous shunt (n=6), trabeculectomy (n=5), and Ex-Press trabeculectomy (n=3). Total protein concentrations were determined with Bradford assay. Tryptic digests were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins were identified with high confidence using stringent criteria and were quantitatively compared with a label-free platform. Relative protein quantities were compared across groups with ANOVA. Post hoc pair-wise comparisons were adjusted for multiple comparisons.

Results: Compared to the control eyes, the aqueous humor protein concentration was increased approximately tenfold in the Ahmed and Baerveldt eyes and fivefold in the trabeculectomy and Ex-Press eyes. Overall, 718 unique proteins, splice variants, or isoforms were identified. No differences in the protein concentrations were detected between the Baerveldt and Ahmed groups. Likewise, the trabeculectomy and Ex-Press groups were remarkably similar. Therefore, the aqueous shunt groups were pooled, and the trabeculectomy groups were pooled for a three-way comparison with the controls. More than 500 proteins differed significantly in relative abundance (ANOVA p<0.01) among the control, aqueous shunt, and trabeculectomy groups. Functional analyses suggested these alterations in relative protein abundance affected dozens of signaling pathways.

Conclusions: Different glaucoma surgical procedures were associated with marked increases in the aqueous humor protein concentration and distinctive changes in the relative abundance of numerous proteins involved in multiple signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aqueous Humor / metabolism*
  • Case-Control Studies
  • Corneal Endothelial Cell Loss / etiology
  • Cross-Sectional Studies
  • Eye Proteins / metabolism*
  • Filtering Surgery / adverse effects
  • Filtering Surgery / methods*
  • Glaucoma / metabolism*
  • Glaucoma / surgery*
  • Glaucoma Drainage Implants / adverse effects
  • Humans
  • Postoperative Complications / etiology
  • Prospective Studies
  • Proteome / metabolism
  • Signal Transduction
  • Tandem Mass Spectrometry
  • Trabeculectomy / adverse effects
  • Trabeculectomy / methods

Substances

  • Eye Proteins
  • Proteome