Distinctive and pervasive alterations in aqueous humor protein composition following different types of glaucoma surgery

Cyril Rosenfeld, Marianne O. Price, Xianyin Lai, Frank Witzmann, Francis W. Price

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose: To investigate whether specific glaucoma surgeries are associated with differences in aqueous humor protein concentrations compared to eyes without filters. Methods: In this cross-sectional study, aqueous humor samples were prospectively collected from control subjects who underwent routine cataract surgery (n=14) and from patients who had different glaucoma filters: Baerveldt aqueous shunt (n=6), Ahmed aqueous shunt (n=6), trabeculectomy (n=5), and Ex-Press trabeculectomy (n=3). Total protein concentrations were determined with Bradford assay. Tryptic digests were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins were identified with high confidence using stringent criteria and were quantitatively compared with a label-free platform. Relative protein quantities were compared across groups with ANOVA. Post hoc pair-wise comparisons were adjusted for multiple comparisons. Results: Compared to the control eyes, the aqueous humor protein concentration was increased approximately tenfold in the Ahmed and Baerveldt eyes and fivefold in the trabeculectomy and Ex-Press eyes. Overall, 718 unique proteins, splice variants, or isoforms were identified. No differences in the protein concentrations were detected between the Baerveldt and Ahmed groups. Likewise, the trabeculectomy and Ex-Press groups were remarkably similar. Therefore, the aqueous shunt groups were pooled, and the trabeculectomy groups were pooled for a three-way comparison with the controls. More than 500 proteins differed significantly in relative abundance (ANOVA p<0.01) among the control, aqueous shunt, and trabeculectomy groups. Functional analyses suggested these alterations in relative protein abundance affected dozens of signaling pathways. Conclusions: Different glaucoma surgical procedures were associated with marked increases in the aqueous humor protein concentration and distinctive changes in the relative abundance of numerous proteins involved in multiple signaling pathways.

Original languageEnglish
Pages (from-to)911-918
Number of pages8
JournalMolecular Vision
Volume21
StatePublished - Aug 25 2015

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Aqueous Humor
Glaucoma
Trabeculectomy
Glaucoma Drainage Implants
Proteins
Analysis of Variance
Protein Isoforms
Tandem Mass Spectrometry
Liquid Chromatography
Cataract
Cross-Sectional Studies

ASJC Scopus subject areas

  • Ophthalmology

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Distinctive and pervasive alterations in aqueous humor protein composition following different types of glaucoma surgery. / Rosenfeld, Cyril; Price, Marianne O.; Lai, Xianyin; Witzmann, Frank; Price, Francis W.

In: Molecular Vision, Vol. 21, 25.08.2015, p. 911-918.

Research output: Contribution to journalArticle

Rosenfeld, Cyril ; Price, Marianne O. ; Lai, Xianyin ; Witzmann, Frank ; Price, Francis W. / Distinctive and pervasive alterations in aqueous humor protein composition following different types of glaucoma surgery. In: Molecular Vision. 2015 ; Vol. 21. pp. 911-918.
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abstract = "Purpose: To investigate whether specific glaucoma surgeries are associated with differences in aqueous humor protein concentrations compared to eyes without filters. Methods: In this cross-sectional study, aqueous humor samples were prospectively collected from control subjects who underwent routine cataract surgery (n=14) and from patients who had different glaucoma filters: Baerveldt aqueous shunt (n=6), Ahmed aqueous shunt (n=6), trabeculectomy (n=5), and Ex-Press trabeculectomy (n=3). Total protein concentrations were determined with Bradford assay. Tryptic digests were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins were identified with high confidence using stringent criteria and were quantitatively compared with a label-free platform. Relative protein quantities were compared across groups with ANOVA. Post hoc pair-wise comparisons were adjusted for multiple comparisons. Results: Compared to the control eyes, the aqueous humor protein concentration was increased approximately tenfold in the Ahmed and Baerveldt eyes and fivefold in the trabeculectomy and Ex-Press eyes. Overall, 718 unique proteins, splice variants, or isoforms were identified. No differences in the protein concentrations were detected between the Baerveldt and Ahmed groups. Likewise, the trabeculectomy and Ex-Press groups were remarkably similar. Therefore, the aqueous shunt groups were pooled, and the trabeculectomy groups were pooled for a three-way comparison with the controls. More than 500 proteins differed significantly in relative abundance (ANOVA p<0.01) among the control, aqueous shunt, and trabeculectomy groups. Functional analyses suggested these alterations in relative protein abundance affected dozens of signaling pathways. Conclusions: Different glaucoma surgical procedures were associated with marked increases in the aqueous humor protein concentration and distinctive changes in the relative abundance of numerous proteins involved in multiple signaling pathways.",
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