Ocular Microbiology and Immunology Group
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2024 OMIG Abstract

Host Immunomodulatory Metabolite RvD1 as Anti-Inflammatory Therapies to Treat Infectious and Non-Infectious Ocular Diseases

Ashok Kumar, Sukhvinder Singh Zeeshan Ahmad, Henry Kolge

Department of Ophthalmology, Visual and Anatomical Sciences, Kresge Eye Institute,
Wayne State University School of Medicine, Detroit, MI

Purpose: Inflammation is a protective host response evoked during injury or microbial Infection. However, persistent inflammation can cause ocular tissue damage, warranting newer non-immunosuppressive anti-inflammatory therapeutic. In this study, we investigated the anti-inflammatory role of a bioactive lipid mediator, resolvin D1 (RvD1), the pathogenesis of infectious (bacterial endophthalmitis) and non-infectious [autoimmune uveitis (AU)], the predominant cause of intraocular inflammation and vision loss.

Methods: Endophthalmitis was induced in wild type C57BL/6 (B6) mice via intravitreal injection of S. aureus. Six hours post-infection, eyes were treated with RvD1. The disease progression was monitored via ophthalmoscopic examination, electroretinography (ERG), histopathological exam, and bacterial burden estimation. AU was induced in B6 mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). Disease severity was assessed based on fundus examination and retinal function (ERG) testing. Ocular tissue (retina) and splenocytes were harvested at 21 days post-immunization. Flow cytometry was used to determine the frequencies of myeloid (macrophages, monocytes, and neutrophils) and lymphoid (Th1, Th17, and Tregs) cells. In vitro, studies were performed using mice splenocytes and challenging them with IRBP in the presence or absence of RvD1. The level of intraocular inflammatory cytokines and chemokines was assessed by qPCR and ELISA.

Results: Intravitreal injection of RvD1 significantly improved the disease outcome as revealed by the drastically reduced bacterial burden, intraocular inflammatory cytokines (IL1β and IL-6), and chemokines (MIP2 and KC), and preserved retinal structure and function. Moreover, RvD1 synergizes with antibiotic to ameliorate bacterial endophthalmitis. In non-infectious AU model, the systemic supplementation of RvD1 improved the uveitis severity and preserved ERG response. Mechanistically, splenocytes treated with RvD1 exhibited enhanced regulatory T cells, and decreased the production of inflammatory mediators.

Conclusions: Our study demonstrates that host metabolite RvD1 exerts anti-inflammatory effects and promotes inflammation resolution during infectious and non-infectious diseases.

Disclosure:

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