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Editors Selection IGR 13-1

Surgical Therapy: Glaucoma shunt and proteins in aqueous

Comment by Sanjoy Bhattacharya on:

46861 Alterations in the aqueous humor proteome in patients with a glaucoma shunt device, Anshu A; Price MO; Richardson MR et al., Molecular Vision, 2011; 17: 1891-1900

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Does implantation of a glaucoma shunt devices cause a breach in bloodaqueous barrier or chronic trauma resulting in accumulation of apoptotic and inflammatory proteins in the aqueous humor (AH) in difference to normal non-glaucomatous controls? The pertinent point is placement of such devices is actually maintenance of a wound and placement of a foreign body. Should such an intervention strategy therefore alter the homeostasis and molecular players? Anshu et al. (1239) asked the question, whether implantation of a glaucoma shunt device results in accumulation of plasma derived proteins in the aqueous humor (AH). They analyzed AH samples from 11 patients with a glaucoma shunt device (nine with Ahmed valve and two eyes with Baerveldt implant) undergoing either cataract surgery or a corneal transplant and 11 control patients with senile cataract undergoing routine cataract extraction with a high accuracy high resolution LTQ Orbitrap mass spectrometer (Thermo Scientific, SanJose, CA) importantly after depletion for albumin and immunoglobulins. In recent times several studies have been conducted to determine differential protein identification using moderate resolution and accuracy mass spectrometers (Duan et al., 2010); protein microarrays (Izzotti et al., 2010) between control and primary open-angle glaucoma (POAG) patients. Tremendous variability has been found by comparative and quantitative (iTRAQ®) analysis of the protein content of AH from cataract (control) patients by mass spectrometry (Bennett et al., 2011) and several novel proteins have been profiled in the AH using high accuracy and resolution (Chowdhury et al., 2010) mass spectrometer with nanoflow front end devices. Tremendous gender variability was also recorded in these quantitative studies.

Presence of anti-inflammatory protein after the shunt devices have been present for a long enough periods perhaps indicates an altered homeostasis

Anshu et al. performed label-free peptide count based quantitative mass spectrometry on AH samples from control and patients with prior glaucoma shunt surgery. This differential approach lacks analyses of glaucoma with and without shunt surgery as control patients are normal subjects with senile cataract surgery. Also, the AH samples were depleted of abundant proteins which has been shown to have undesirable elimination of co-eluting proteins and peptides with abundant proteins. Their identification of 135 proteins in the albumin-depleted fraction is lower than similar analyses. The AH in eyes with a prior glaucoma shunt device showed significantly increased levels of 13 proteins: plasminogen, angiotensinogen, prothrombin, C4a protein, gelsolin, afamin, pigment epitheliumderived factor, dickkopf-3 protein, apolipoprotein A-I, apolipoprotein A-II, fibronectin 1, RIG-like 7‐1, and beta-2-microglobulin. These protein cohorts include both pro- and anti-inflammatory proteins as well as proteins which do not belong to either of these groups. Thus Anshu et al. asks a pertinent question whether levels of apoptotic and inflammatory proteins are increased due to placement of a glaucoma shunt device, which is akin to keeping a wound and a foreign body. However, presence of anti-inflammatory protein after the shunt devices have been present for a long enough periods perhaps indicates an altered homeostasis. It is an interesting point and greater insight about molecular changes to current intervention strategies will benefit for suitable modification of intervention strategies or construction of new devices. Further work and a better capture will enable better coverage of identified proteins, for example, ion fractionation and ion mobility mass spectrometry devices hold the promise to avoid abundant protein depletion while enabling better identification of low and high abundance proteins simultaneously. Analyses of molecular changes due to shunts explored in animal models will also provide greater insight into altered homoeostasis for long term foreign body presence such as the glaucoma shunt devices.

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