Evaluation of Uveitis Induced in Rats by a Type I Collagen Peptide as a Model for Childhood Arthritis-associated Uveitis-Reference-Cited by-同舟云学术

Evaluation of Uveitis Induced in Rats by a Type I Collagen Peptide as a Model for Childhood Arthritis-associated Uveitis

Published:2023-08-27 Issue:4 Volume:73 Page:267-276
ISSN:1532-0820
Container-title:Comparative Medicine
language:en
Short-container-title:comp med

Author:

Osinchuk Stephanie C¹,Grahn Bruce H¹,Wilson Tracy D²,Thompson Brooke N³,Hart David A⁴,Harrison Kim D⁵,Cooper David ML⁵,Panahifar Arash⁶,Rosenberg Alan M⁷

Affiliation:

1. Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;

2. Department of Pediatrics, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;

3. Canadian Centre for Health and Safety in Agriculture, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;

4. Department of Surgery, University of Calgary, Calgary, Alberta, Canada;

5. Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan; Saskatoon, Saskatchewan, Canada;

6. Canadian Light Source, Saskatoon, Saskatchewan, Canada; Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

7. Department of Pediatrics, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Corresponding author. alan. rosenberg@usask. ca

Abstract

Chronic asymptomatic and acute symptomatic anterior uveitis are forms of ocular inflammation associated with juvenile idiopathic arthritis (JIA) Chronic JIA-associated uveitis is characterized by young age of onset, female predilection, oligoarthritis, and antinuclear antibody (ANA) positivity. Acute JIA-associated uveitis predominantly affects older male juveniles who also develop enthesitis. A type I collagen-derived peptide (melanin-associated antigen [MAA]) induces anterior uveitis in rodents. In this study, we evaluated MAA-induced uveitis in rats as a potential model for JIA-uveitis. We characterized MAA-induced uveitis by assessing its relationship to age and sex; tracking the occurrence of arthritis, enthesitis, and ANA positivity; and measuring vitreous fluid inflammatory biomarkers. Juvenile and adult and male and female Lewis rats (Rattus norvegicus) were inoculated with MAA. Slit-lamp biomicroscopy, indirect ophthalmoscopy, and joint examinations were performed 3 times weekly. Rats were euthanized at 4 wk after MAA inoculation, and plasma ANA testing, vitreous inflammatory biomarker assays, and globe histopathology assessments were conducted. Uveitis, arthritis, ANA status, levels of inflammatory biomarkers, histopathology, and joint tomographic images were assessed in relation to age and sex and compared with nonuveitic controls. All MAA-immunized rats developed uveitis characterized by anterior chamber fibrin, iridal vessel dilation, and miosis, and uveal and choroidal lymphocytic infiltration. Levels of the vitreous fluid biomarker CCL5 were higher in uveitic rats compared with control rats. Time to uveitis onset, clinical uveitis scores, and biomarker levels did not differ based on age or sex. None of the MAA-exposed rats had arthritis, enthesitis, or ANA. None of the rats inoculated with MAA that had been treated with matrix metallopeptidase 1 had clinical, histologic, or immunohistochemical evidence of ocular inflammation. In contrast to JIA-associated uveitis in humans, MAA-induced uveitis in rats is not associated with age or sex predilections and MAA is not arthritogenic.

Publisher

American Association for Laboratory Animal Science

Subject

General Veterinary,General Biochemistry, Genetics and Molecular Biology

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