Compositional Analysis of Extracellular Aggregates in the Eyes of Patients With Exfoliation Syndrome and Exfoliation Glaucoma.
De Maria Alicia, Zientek Keith D, David Larry L, Wilmarth Phillip A, Bhorade Anjali M, Harocopos George J, Huang Andrew J W, Hong Augustine R, Siegfried Carla J, Tsai Linda M
AI Summary
Researchers analyzed exfoliation material composition, finding consistent proteins like fibrillin-1 and LEFTY2. Elevated LEFTY2 in aqueous humor may be a biomarker for 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.
MeSH Terms
Shields Classification
Key Concepts4
Quantitative mass spectrometry analysis of lens capsule samples from patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) consistently upregulated fibrillin-1, latent transforming growth factor-β-binding protein-2, and latent transforming growth factor-β-binding protein-3.
Lysyl oxidase-like 1 was an abundant constituent of exfoliation material (XFM) in lens capsule samples from patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG), as determined by quantitative mass spectrometry.
Elevated levels of LEFTY2 were detected in aqueous humor (AH) from patients with exfoliation glaucoma (XFG), a finding confirmed by ELISA, suggesting its potential as a biomarker.
The consistent exfoliation material (XFM) proteome in patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) is characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2, as revealed by quantitative mass spectrometry.
Related Articles5
Assessment of corneal topographic, tomographic, densitometric, and biomechanical properties of Fabry patients with ocular manifestations.
Cross-Sectional StudyScreening glaucoma genes in adult glaucoma suggests a multiallelic contribution of CYP1B1 to open-angle glaucoma phenotypes.
Case SeriesComprehensive Proteomic Profiling of Exfoliation Glaucoma Via Mass Spectrometry Reveals SVEP1 as a Potential Biomarker.
Cohort StudyConjunctival lymphangiectasia as a biomarker of severe systemic disease in Ser77Tyr hereditary transthyretin amyloidosis.
Cross-Sectional StudyOphthalmic manifestations in a Chinese family with familial amyloid polyneuropathy due to a TTR Gly83Arg mutation.
Case SeriesIs this article assigned to the wrong chapter(s)? Let us know.