title: Alterations in the aqueous humor proteome in patients with a glaucoma shunt device.
abstract: OBJECTIVE
  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.
authors.affiliation: Price Vision Group, Indianapolis, IN, USA.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Anshu
authors.forename: Marianne O
authors.initials: MO
authors.lastname: Price
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Richardson
authors.forename: Zaneer M
authors.initials: ZM
authors.lastname: Segu
authors.forename: Xianyin
authors.initials: X
authors.lastname: Lai
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
authors.forename: Francis W
authors.initials: FW
authors.lastname: Price
mesh_terms: D000328:Adult; D000368:Aged; D001082:Aqueous Humor / Q000737:chemistry / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis*; D018916:Blood-Aqueous Barrier / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002386:Cataract / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002387:Cataract Extraction; D002853:Chromatography, Liquid; D005260:Female; D005901:Glaucoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D020327:Glaucoma Drainage Implants / Q000009:adverse effects*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D021381:Protein Transport / Q000187:drug effects; D020543:Proteome / Q000032:analysis*; D053719:Tandem Mass Spectrometry
chemical_list: D001798:Blood Proteins; D020543:Proteome