Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target

Purpose: To profile vitreous protein expression of intermediate uveitis (IU) patients. Observations: We identified a mean of 363 ± 41 unique proteins (mean ± SD) in IU vitreous and 393 ± 69 unique proteins in control samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of...

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Main Authors: Yasir J. Sepah, Gabriel Velez, Peter H. Tang, Jing Yang, Teja Chemudupati, Angela S. Li, Quan D. Nguyen, Alexander G. Bassuk, Vinit B. Mahajan
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:American Journal of Ophthalmology Case Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2451993619300155
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spelling doaj-0b8b1149c276416785f871974a58d5c22020-11-25T03:32:05ZengElsevierAmerican Journal of Ophthalmology Case Reports2451-99362020-06-0118Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic targetYasir J. Sepah0Gabriel Velez1Peter H. Tang2Jing Yang3Teja Chemudupati4Angela S. Li5Quan D. Nguyen6Alexander G. Bassuk7Vinit B. Mahajan8Omics Laboratory, Stanford University, Palo Alto, CA, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USAOmics Laboratory, Stanford University, Palo Alto, CA, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA; Medical Scientist Training Program, University of Iowa, Iowa City, IA, USAOmics Laboratory, Stanford University, Palo Alto, CA, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USAOmics Laboratory, Stanford University, Palo Alto, CA, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USAOmics Laboratory, Stanford University, Palo Alto, CA, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USAOmics Laboratory, Stanford University, Palo Alto, CA, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USADepartment of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USADepartment of Pediatrics, University of Iowa, Iowa City, IA, USAOmics Laboratory, Stanford University, Palo Alto, CA, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Corresponding author. Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CA, 94304, USA.Purpose: To profile vitreous protein expression of intermediate uveitis (IU) patients. Observations: We identified a mean of 363 ± 41 unique proteins (mean ± SD) in IU vitreous and 393 ± 69 unique proteins in control samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of liquid vitreous biopsies collected during pars plana vitrectomy. A total of 233 proteins were differentially expressed among control and IU samples, suggesting a protein signature that could distinguish the two groups. Pathway analysis identified 22 inflammatory mediators of the interleukin-12 (IL-12) signaling pathway in IU vitreous. Upstream regulator analysis identified downstream mediators of IL-23 and myeloid differentiation primary response protein (MYD88), both of which are involved in the recruitment and differentiation of myeloid cells. Taken together, our results suggest the recruitment of myeloid cells as an upstream pathway in the pathogenesis of IU. Conclusions: This study provides insights into proteins that will serve as biomarkers and therapeutic targets for IU. These biomarkers will help design future clinical trials using rational molecular therapeutics.http://www.sciencedirect.com/science/article/pii/S2451993619300155ProteomicsVitreousBiomarkerIntermediate uveitis
collection DOAJ
language English
format Article
sources DOAJ
author Yasir J. Sepah
Gabriel Velez
Peter H. Tang
Jing Yang
Teja Chemudupati
Angela S. Li
Quan D. Nguyen
Alexander G. Bassuk
Vinit B. Mahajan
spellingShingle Yasir J. Sepah
Gabriel Velez
Peter H. Tang
Jing Yang
Teja Chemudupati
Angela S. Li
Quan D. Nguyen
Alexander G. Bassuk
Vinit B. Mahajan
Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target
American Journal of Ophthalmology Case Reports
Proteomics
Vitreous
Biomarker
Intermediate uveitis
author_facet Yasir J. Sepah
Gabriel Velez
Peter H. Tang
Jing Yang
Teja Chemudupati
Angela S. Li
Quan D. Nguyen
Alexander G. Bassuk
Vinit B. Mahajan
author_sort Yasir J. Sepah
title Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target
title_short Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target
title_full Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target
title_fullStr Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target
title_full_unstemmed Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target
title_sort proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates il-23 as a therapeutic target
publisher Elsevier
series American Journal of Ophthalmology Case Reports
issn 2451-9936
publishDate 2020-06-01
description Purpose: To profile vitreous protein expression of intermediate uveitis (IU) patients. Observations: We identified a mean of 363 ± 41 unique proteins (mean ± SD) in IU vitreous and 393 ± 69 unique proteins in control samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of liquid vitreous biopsies collected during pars plana vitrectomy. A total of 233 proteins were differentially expressed among control and IU samples, suggesting a protein signature that could distinguish the two groups. Pathway analysis identified 22 inflammatory mediators of the interleukin-12 (IL-12) signaling pathway in IU vitreous. Upstream regulator analysis identified downstream mediators of IL-23 and myeloid differentiation primary response protein (MYD88), both of which are involved in the recruitment and differentiation of myeloid cells. Taken together, our results suggest the recruitment of myeloid cells as an upstream pathway in the pathogenesis of IU. Conclusions: This study provides insights into proteins that will serve as biomarkers and therapeutic targets for IU. These biomarkers will help design future clinical trials using rational molecular therapeutics.
topic Proteomics
Vitreous
Biomarker
Intermediate uveitis
url http://www.sciencedirect.com/science/article/pii/S2451993619300155
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