دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Compositional Analysis of Extracellular Aggregates in the Eyes of Patients With Exfoliation Syndrome and Exfoliation Glaucoma.
المؤلفون: De Maria A; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States., Zientek KD; Proteomics Shared Resource, Oregon Health and Science University, Portland, Oregon, United States., David LL; Department of Chemical Physiology & Biochemistry, Oregon Health and Science University, Portland, Oregon, United States., Wilmarth PA; Proteomics Shared Resource, Oregon Health and Science University, Portland, Oregon, United States., Bhorade AM; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States., Harocopos GJ; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, United States., Huang AJW; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States., Hong AR; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States., Siegfried CJ; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States., Tsai LM; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States., Sheybani A; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States., Bassnett S; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
المصدر: Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2021 Dec 01; Vol. 62 (15), pp. 27.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Association For Research In Vision And Ophthalmology (Arvo) Country of Publication: United States NLM ID: 7703701 Publication Model: Print Cited Medium: Internet ISSN: 1552-5783 (Electronic) Linking ISSN: 01460404 NLM ISO Abbreviation: Invest Ophthalmol Vis Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: Brookline Ma : Association For Research In Vision And Ophthalmology (Arvo)
Original Publication: St. Louis, Mosby.
مواضيع طبية MeSH: Aqueous Humor/*metabolism , Crystallins/*metabolism , Exfoliation Syndrome/*metabolism , Glaucoma, Open-Angle/*metabolism , Lens Capsule, Crystalline/*metabolism , Protein Aggregates/*physiology, Aged ; Aged, 80 and over ; Amino Acid Oxidoreductases/metabolism ; Chromatography, High Pressure Liquid ; Crystallins/ultrastructure ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrillin-1/metabolism ; Fluorescent Antibody Technique, Indirect ; Humans ; Latent TGF-beta Binding Proteins/metabolism ; Left-Right Determination Factors/metabolism ; Lens Capsule, Crystalline/ultrastructure ; Male ; Mass Spectrometry ; Microscopy, Electron, Scanning ; Middle Aged
مستخلص: 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.
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معلومات مُعتمدة: P30 EY002687 United States EY NEI NIH HHS; P30 EY010572 United States EY NEI NIH HHS; R01 EY009852 United States EY NEI NIH HHS; S10 OD012246 United States OD NIH HHS; R01 EY029130 United States EY NEI NIH HHS; P30 CA069533 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Crystallins)
0 (FBN1 protein, human)
0 (Fibrillin-1)
0 (LEFTY2 protein, human)
0 (LTBP2 protein, human)
0 (LTBP3 protein, human)
0 (Latent TGF-beta Binding Proteins)
0 (Left-Right Determination Factors)
0 (Protein Aggregates)
EC 1.4.- (Amino Acid Oxidoreductases)
EC 1.4.3.- (LOXL1 protein, human)
تواريخ الأحداث: Date Created: 20211229 Date Completed: 20220114 Latest Revision: 20220116
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8740535
DOI: 10.1167/iovs.62.15.27
PMID: 34964803
قاعدة البيانات: MEDLINE
الوصف
تدمد:1552-5783
DOI:10.1167/iovs.62.15.27