Compositional Analysis of Extracellular Aggregates in the Eyes of Patients with Exfoliation Syndrome and Exfoliation Glaucoma

Alicia de Maria; Keith D. Zientek; Larry L. David; Phillip A. Wilmarth; Anjali M. Bhorade; George J. Harocopos; Andrew J.W. Huang; Augustine R. Hong; Carla J. Siegfried; Linda M. Tsai; Arsham Sheybani; Steven Bassnett

doi:10.1167/iovs.62.15.27

Compositional Analysis of Extracellular Aggregates in the Eyes of Patients with Exfoliation Syndrome and Exfoliation Glaucoma

Alicia de Maria, Keith D. Zientek, Larry L. David, Phillip A. Wilmarth, Anjali M. Bhorade, George J. Harocopos, Andrew J.W. Huang, Augustine R. Hong, Carla J. Siegfried, Linda M. Tsai, Arsham Sheybani, Steven Bassnett

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

PURPOSE: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. METHODS. Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. RESULTS. A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-β-binding protein-2 and latent transforming growth factor-β-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-β superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. CONCLUSIONS. This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.

Original language	English (US)
Article number	27
Journal	Investigative Ophthalmology and Visual Science
Volume	62
Issue number	15
DOIs	https://doi.org/10.1167/iovs.62.15.27
State	Published - Dec 2021

Keywords

Exfoliation
Glaucoma
LEFTY2
Proteome
Syndrome

ASJC Scopus subject areas

Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience

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10.1167/iovs.62.15.27

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de Maria, A., Zientek, K. D., David, L. L., Wilmarth, P. A., Bhorade, A. M., Harocopos, G. J., Huang, A. J. W., Hong, A. R., Siegfried, C. J., Tsai, L. M., Sheybani, A., & Bassnett, S. (2021). Compositional Analysis of Extracellular Aggregates in the Eyes of Patients with Exfoliation Syndrome and Exfoliation Glaucoma. Investigative Ophthalmology and Visual Science, 62(15), Article 27. https://doi.org/10.1167/iovs.62.15.27

de Maria, A, Zientek, KD, David, LL, Wilmarth, PA, Bhorade, AM, Harocopos, GJ, Huang, AJW, Hong, AR, Siegfried, CJ, Tsai, LM, Sheybani, A & Bassnett, S 2021, 'Compositional Analysis of Extracellular Aggregates in the Eyes of Patients with Exfoliation Syndrome and Exfoliation Glaucoma', Investigative Ophthalmology and Visual Science, vol. 62, no. 15, 27. https://doi.org/10.1167/iovs.62.15.27

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title = "Compositional Analysis of Extracellular Aggregates in the Eyes of Patients with Exfoliation Syndrome and Exfoliation Glaucoma",

abstract = "PURPOSE: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. METHODS. Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. RESULTS. A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-β-binding protein-2 and latent transforming growth factor-β-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-β superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. CONCLUSIONS. This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.",

keywords = "Exfoliation, Glaucoma, LEFTY2, Proteome, Syndrome",

author = "{de Maria}, Alicia and Zientek, {Keith D.} and David, {Larry L.} and Wilmarth, {Phillip A.} and Bhorade, {Anjali M.} and Harocopos, {George J.} and Huang, {Andrew J.W.} and Hong, {Augustine R.} and Siegfried, {Carla J.} and Tsai, {Linda M.} and Arsham Sheybani and Steven Bassnett",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors iovs.arvojournals.org",

year = "2021",

month = dec,

doi = "10.1167/iovs.62.15.27",

language = "English (US)",

volume = "62",

journal = "Investigative Ophthalmology and Visual Science",

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publisher = "Association for Research in Vision and Ophthalmology Inc.",

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T1 - Compositional Analysis of Extracellular Aggregates in the Eyes of Patients with Exfoliation Syndrome and Exfoliation Glaucoma

AU - de Maria, Alicia

AU - Zientek, Keith D.

AU - David, Larry L.

AU - Wilmarth, Phillip A.

AU - Bhorade, Anjali M.

AU - Harocopos, George J.

AU - Huang, Andrew J.W.

AU - Hong, Augustine R.

AU - Siegfried, Carla J.

AU - Tsai, Linda M.

AU - Sheybani, Arsham

AU - Bassnett, Steven

PY - 2021/12

Y1 - 2021/12

N2 - PURPOSE: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. METHODS. Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. RESULTS. A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-β-binding protein-2 and latent transforming growth factor-β-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-β superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. CONCLUSIONS. This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.

AB - PURPOSE: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. METHODS. Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. RESULTS. A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-β-binding protein-2 and latent transforming growth factor-β-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-β superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. CONCLUSIONS. This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.

KW - Exfoliation

KW - Glaucoma

KW - LEFTY2

KW - Proteome

KW - Syndrome

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Compositional Analysis of Extracellular Aggregates in the Eyes of Patients with Exfoliation Syndrome and Exfoliation Glaucoma

Abstract

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