Compositional analysis of extracellular aggregates in the eyes of patients with exfoliation syndrome and exfoliation glaucoma.

ABSTRACT: 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 aqueous humor samples from XFS and XFG patients and individuals without XFS. Pieces of lens capsule and samples of aqueous humor were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or aqueous samples were analyzed by HPLC-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 scanning electron microscopy and super-resolution light microscopy. A small set of proteins was consistently upregulated in XFS samples, including microfibril components fibrillin-1 (FBN1), latent TGFBeta-binding protein-2 (LTBP-2), and LTBP-3. Lysyl oxidase-like 1 (LOXL1), a protein linked strongly to XFS in genetic studies, was an abundant XFM protein. Ligands of the TGFBeta superfamily were prominent, including LEFTY2, a protein known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in aqueous humor from XFG patients and confirmed by ELISA. This analysis verified the presence of several suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome. The expression of FBN1, LOXL1, and LEFTY2 was particularly strong in XFG patients in comparison to XFS patients.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Eye, Lens

DISEASE(S): Exfoliation Syndrome

SUBMITTER: Phillip Wilmarth  

LAB HEAD: Dr. Steven Bassnett

PROVIDER: PXD026764 | Pride | 2022-02-17

REPOSITORIES: pride