Alterations in the aqueous humor proteome in patients with a glaucoma shunt device

Mol Vis. 2011;17:1891-900. Epub 2011 Jul 14.

Abstract

Purpose: To investigate whether implantation of a glaucoma shunt device leads to inappropriate accumulation of plasma derived proteins in the aqueous humor.

Methods: Aqueous humor samples were collected from 11 patients (study group) with a glaucoma shunt device undergoing either cataract surgery or a corneal transplant and 11 patients (control) with senile cataract undergoing routine cataract extraction. Of the study group, 9 had an Ahmed valve implant and 2 eyes had a Baerveldt implant. Tryptic digests of the mixture of proteins in aqueous humor (AH) were analyzed using Liquid Chromatography/Mass Spectrometry (LC-MS/MS). Proteins were identified with high confidence using stringent criteria and compared quantitatively using a label-free platform (IdentiQuantXL™).

Results: We identified 135 proteins in the albumin-depleted fraction in both the study and control group AH. Using stringent criteria, 13 proteins were detected at a significantly higher level compared to controls. These proteins are known to play a role in oxidative stress, apoptosis, inflammation and/or immunity and include gelsolin (p=0.00005), plasminogen (p=0.00009), angiotensinogen (p=0.0001), apolipoprotein A-II (p=0.0002), beta-2-microglobulin (p=0.0002), dickkopf-3 (DKK-3; p=0.0002), pigment epithelium-derived factor (p=0.0002), RIG-like 7-1 (p=0.0002), afamin (p=0.0003), fibronectin 1 (FN1; p=0.0003), apolipoprotein A-I (p=0.0004), activated complement C4 protein (C4a; p=0.0004) and prothrombin (p=0.0004). Many of the identified proteins were novel proteins that have not been associated with glaucoma in prior studies. All but C4a (complement C4 is a plasma protein but not in an activated form) are known plasma proteins and the elevated levels of these proteins in the aqueous humor suggests a breach in the blood-aqueous barrier with passive influx into the anterior chamber of the eye.

Conclusions: The presence of these proteins in the aqueous humor suggests that glaucoma shunt device causes either a breach in blood-aqueous barrier or chronic trauma, increasing influx of oxidative, apoptotic and inflammatory proteins that could potentially cause corneal endothelial damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aqueous Humor / chemistry
  • Aqueous Humor / metabolism*
  • Blood Proteins / analysis*
  • Blood-Aqueous Barrier / metabolism*
  • Blood-Aqueous Barrier / pathology
  • Case-Control Studies
  • Cataract / complications
  • Cataract / metabolism*
  • Cataract / pathology
  • Cataract Extraction
  • Chromatography, Liquid
  • Female
  • Glaucoma / complications
  • Glaucoma / metabolism*
  • Glaucoma / pathology
  • Glaucoma / surgery
  • Glaucoma Drainage Implants / adverse effects*
  • Humans
  • Lens, Crystalline / metabolism*
  • Lens, Crystalline / pathology
  • Lens, Crystalline / surgery
  • Male
  • Middle Aged
  • Protein Transport / drug effects
  • Proteome / analysis*
  • Tandem Mass Spectrometry

Substances

  • Blood Proteins
  • Proteome