The inflammatory response in aqueous humor from horses with uveitis

This study helps characterize the nature of the inflammatory response in the eyes of horses with recurrent uveitis. Understanding this helps develop more effective therapies for a disease that is prevalent and expensive to manage and treat. Specifically, treatments that aim at proinflammatory cytokines and the complement cascade have the potential as therapeutic targets for equine uveitis. Some of these would include tumor necrosis factor inhibitors, antagonizing interleukins, interferons, and Janus kinases are possibilities that need studies to determine their value.
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The use of shotgun label-free quantitative proteomic mass spectrometry to evaluate the inflammatory response in aqueous humor from horses with uveitis compared to ophthalmologically healthy horses
Vet Ophthalmol. 2023 May 5. doi: 10.1111/vop.13107. Online ahead of print.
Authors
Hannah M Terhaar 1 , Michala de Linde Henriksen 1 , Carolina Mehaffy 2 , Ann Hess 3 , Richard J McMullen Jr 4
Affiliations

1 Comparative Ophthalmology, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
2 Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
3 Department of Statistics, College of Natural Sciences, Colorado State University, Fort Collins, Colorado, USA.
4 Equine Ophthalmology, Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, JT Vaughan Large Animal Teaching Hospital, Auburn, Alabama, USA.

PMID: 37144658
DOI: 10.1111/vop.13107

Abstract

Objective: The objective of this study was to use shotgun label-free tandem mass spectrometry (LF-MS/MS) to evaluate aqueous humor (AH) from horses with uveitis (UH) compared to ophthalmologically healthy horses (HH).

Animals studied: Twelve horses diagnosed with uveitis based on ophthalmic examination and six ophthalmologically healthy horses (postmortem) purchased for teaching purposes.

Procedures: All horses received a complete ophthalmic examination and physical exam. Aqueous paracentesis was performed on all horses and AH total protein concentrations were measured with nanodrop (TPn) and refractometry (TPr). AH samples were analyzed with shotgun LF-MS/MS and proteomic data were compared between groups using Wilcoxon rank-sum test.

Results: A total of 147 proteins were detected, 11 proteins had higher abundance in UH, and 38 proteins had lower abundance in UH. Proteins with higher abundance included apolipoprotein E, alpha-2-macroglobulin (A2M), alpha-2-HS-glycoprotein, prothrombin, fibrinogen, complement component 4 (C4), joining chain for IgA and IgM, afamin, and amine oxidase. There were positive correlations between TPn (p = .003) and TPr (p = .0001) compared to flare scores.

Conclusion: Differential abundance of A2M, prothrombin, fibrinogen, and C4 indicate upregulation of the complement and coagulation cascade in equine uveitis. Proinflammatory cytokines and the complement cascade have potential as therapeutic targets for equine uveitis.

Keywords: complement; cytokines; diagnostics; equine; equine recurrent uveitis; proteomics.

© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.