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

Arundhati Anshu, Marianne O. Price, Matthew R. Richardson, Zaneer M. Segu, Xianyin Lai, Mervin Yoder, Francis W. Price

Research output: Contribution to journalArticle

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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 (LCMS/ MS). Proteins were identified with high confidence using stringent criteria and compared quantitatively using a labelfree platform (IdentiQuantXL TM). 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.

Original languageEnglish
Pages (from-to)1891-1900
Number of pages10
JournalMolecular Vision
Volume17
StatePublished - 2011

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Aqueous Humor
Proteome
Glaucoma
Equipment and Supplies
Proteins
Blood-Aqueous Barrier
Complement C4
Blood Proteins
Cataract
Glaucoma Drainage Implants
Gelsolin
Apolipoprotein A-II
beta 2-Microglobulin
Angiotensinogen
Cataract Extraction
Plasminogen
Apolipoprotein A-I
Anterior Chamber
Prothrombin
Fibronectins

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Anshu, A., Price, M. O., Richardson, M. R., Segu, Z. M., Lai, X., Yoder, M., & Price, F. W. (2011). Alterations in the aqueous humor proteome in patients with a glaucoma shunt device. Molecular Vision, 17, 1891-1900.

Alterations in the aqueous humor proteome in patients with a glaucoma shunt device. / Anshu, Arundhati; Price, Marianne O.; Richardson, Matthew R.; Segu, Zaneer M.; Lai, Xianyin; Yoder, Mervin; Price, Francis W.

In: Molecular Vision, Vol. 17, 2011, p. 1891-1900.

Research output: Contribution to journalArticle

Anshu, A, Price, MO, Richardson, MR, Segu, ZM, Lai, X, Yoder, M & Price, FW 2011, 'Alterations in the aqueous humor proteome in patients with a glaucoma shunt device', Molecular Vision, vol. 17, pp. 1891-1900.
Anshu A, Price MO, Richardson MR, Segu ZM, Lai X, Yoder M et al. Alterations in the aqueous humor proteome in patients with a glaucoma shunt device. Molecular Vision. 2011;17:1891-1900.
Anshu, Arundhati ; Price, Marianne O. ; Richardson, Matthew R. ; Segu, Zaneer M. ; Lai, Xianyin ; Yoder, Mervin ; Price, Francis W. / Alterations in the aqueous humor proteome in patients with a glaucoma shunt device. In: Molecular Vision. 2011 ; Vol. 17. pp. 1891-1900.
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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 (LCMS/ MS). Proteins were identified with high confidence using stringent criteria and compared quantitatively using a labelfree platform (IdentiQuantXL TM). 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.",
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AU - Yoder, Mervin

AU - Price, Francis W.

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N2 - 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 (LCMS/ MS). Proteins were identified with high confidence using stringent criteria and compared quantitatively using a labelfree platform (IdentiQuantXL TM). 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.

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