Proteomic Alterations in Aqueous Humor From Patients With Primary Open Angle Glaucoma

Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2635-2643. doi: 10.1167/iovs.17-23434.

Abstract

Purpose: Primary open angle glaucoma (POAG) is the most prevalent form of glaucoma, accounting for approximately 90% of all cases. The aqueous humor (AH), a biological fluid in the anterior and posterior chambers of the eye, is involved in a multitude of functions including the maintenance of IOP and ocular homeostasis. This fluid is very close to the pathologic site and is also known to have a significant role in glaucoma pathogenesis. The purpose of this study was to identify proteomic alterations in AH from patients with POAG.

Methods: AH samples were extracted from 47 patients undergoing cataract surgery (controls: n = 32; POAG: n = 15). Proteomic analysis of the digested samples was accomplished by liquid-chromatography-mass spectrometry. The identified proteins were evaluated using a variety of statistical and bioinformatics methods.

Results: A total of 33 proteins were significantly altered in POAG subjects compared with the controls. The most abundant proteins in POAG subjects are IGKC (13.56-fold), ITIH4 (4.1-fold), APOC3 (3.36-fold), IDH3A (3.11-fold), LOC105369216 (2.98-fold). SERPINF2 (2.94-fold), NPC2 (2.88-fold), SUCLG2 (2.70-fold), KIAA0100 (2.29-fold), CNOT4 (2.23-fold), AQP4 (2.11-fold), COL18A1 (2.08-fold), NWD1 (2.07-fold), and TMEM120B (2.06-fold). A significant increasing trend in the odds ratios of having POAG was observed with increased levels of these proteins.

Conclusion: Proteins identified in this study are implicated in signaling, glycosylation, immune response, molecular transport, and lipid metabolism. The identified candidate proteins may be potential biomarkers associated with POAG development and may lead to more insight in understanding the mechanisms underlying the pathogenesis of this disease.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aqueous Humor / metabolism*
  • Biomarkers / metabolism
  • Cataract Extraction
  • Chromatography, Liquid
  • Eye Proteins / metabolism*
  • Female
  • Glaucoma, Open-Angle / metabolism*
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Proteomics
  • Transcription Factors / metabolism

Substances

  • Biomarkers
  • Eye Proteins
  • Transcription Factors