Proteomic Analysis of Autoimmune Retinopathy Implicates Neuronal Cell Adhesion Molecule as a Potential Biomarker

Ahmad Al-Moujahed, MD, PhD; Gabriel Velez, PhD; Jennifer T. Vu, BS; Jose R. Lima de Carvalho, MD; Sarah R. Levi, BA; Alexander G. Bassuk, MD, PhD; Yasir J. Sepah, MBBS; Stephen H. Tsang, MD, PhD; Vinit B. Mahajan, MD, PhD

Ophthalmology Science (Jun 2022)

Proteomic Analysis of Autoimmune Retinopathy Implicates Neuronal Cell Adhesion Molecule as a Potential Biomarker

Ahmad Al-Moujahed, MD, PhD,
Gabriel Velez, PhD,
Jennifer T. Vu, BS,
Jose R. Lima de Carvalho, MD,
Sarah R. Levi, BA,
Alexander G. Bassuk, MD, PhD,
Yasir J. Sepah, MBBS,
Stephen H. Tsang, MD, PhD,
Vinit B. Mahajan, MD, PhD

Affiliations

Ahmad Al-Moujahed, MD, PhD: Molecular Surgery Laboratory, Stanford University, Palo Alto, California; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California
Gabriel Velez, PhD: Molecular Surgery Laboratory, Stanford University, Palo Alto, California; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California; Medical Scientist Training Program, University of Iowa, Iowa City, Iowa
Jennifer T. Vu, BS: Molecular Surgery Laboratory, Stanford University, Palo Alto, California; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California
Jose R. Lima de Carvalho, MD: Department of Ophthalmology, Columbia University, New York, New York
Sarah R. Levi, BA: Department of Ophthalmology, Columbia University, New York, New York
Alexander G. Bassuk, MD, PhD: Department of Pediatrics, University of Iowa, Iowa City, Iowa
Yasir J. Sepah, MBBS: Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California
Stephen H. Tsang, MD, PhD: Department of Ophthalmology, Columbia University, New York, New York
Vinit B. Mahajan, MD, PhD: Molecular Surgery Laboratory, Stanford University, Palo Alto, California; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Correspondence: Vinit B. Mahajan, MD, PhD, Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CA 94304.

Journal volume & issue: Vol. 2, no. 2
p. 100131

Abstract

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Purpose: To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR). Design: Case-control study. Participants: We analyzed 6 eyes from 4 patients diagnosed with AIR and 8 comparative controls diagnosed with idiopathic macular holes (IMHs) and epiretinal membranes (ERMs). Methods: Vitreous biopsies were collected from the participants and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) or multiplex enzyme-linked immunoassay (ELISA). Main Outcome Measures: Protein expression changes were evaluated by 1-way analysis of variance (significant P value < 0.05), hierarchical clustering, and pathway analysis to identify candidate protein biomarkers. Results: There were 16 significantly upregulated and 17 significantly downregulated proteins in the vitreous of 3 patients with AIR compared with controls. The most significantly upregulated proteins included lysozyme C, zinc-alpha-2-glycoprotein, complement factor D, transforming growth factor-ß (TGF-ß)–induced protein, beta-crystallin B2, and alpha-crystallin A chain. The most significantly downregulated proteins included DIP2C, retbindin, and amyloid beta precursor-like protein 2. Pathway analysis revealed that vascular endothelial growth factor (VEGF) signaling was a top represented pathway in the vitreous of patients with AIR compared with controls. In comparison with a different cohort of 3 patients with AIR analyzed by multiplex ELISA, a commonly differentially expressed protein was neuronal cell adhesion molecule (NrCAM) with P values of 0.027 in the LC-MS/MS dataset and 0.035 in the ELISA dataset. Conclusions: Protein biomarkers in the vitreous, such as NrCAM, may eventually help diagnose AIR.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

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