Abstract

Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse models of dry-eye disease and ocular allergy. Since antigen-presentation is the central similarity in the pathologies, this study focuses on antigen-presentation in CALT Morphology and the expression of CALT, which was investigated in mice after induction of dry-eye, ocular allergy, topical antigen-stimulation, and after local depletion of phagocytic cells. Antigen uptake was investigated after the application of fluorescent ovalbumin (OVA). OSD influences the appearance and morphology of CALT in a disease-dependent manner. Ocular allergy leads to an increase and dry-eye disease to a decrease in number and size of CALT. The development of CALT is dependent on the presence of APCs. Professional APCs are present in CALT, and soluble antigen is transported into the follicle. CALT appearance is disease-specific and indicative of differing functions. Although the specific involvement of CALT in OSD needs further study, the existence of functional APCS and antigen-uptake supports the hypothesis that CALT is an immunological key player at the ocular surface.

Highlights

  • Dry eye disease and ocular allergy are ocular surface inflammatory pathologies with high clinical relevance

  • eye disease (EDE) did not change the presence of CALT compared to naïve mice, but resulted in a significant reduction of the size compared to naïve mice, and SRW, and OVA/CtB treated mice (Figure 1B)

  • In EDE eyes, only a few Antigen-presenting cells (APCs) were present in CALT (Figure 2C, schematic drawing of CALT based on detailed histological analyses)

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Summary

Introduction

Dry eye disease and ocular allergy are ocular surface inflammatory pathologies with high clinical relevance. Dry eye disease is a T-cell driven disease in which autoantigens ( still not fully identified) are discussed to play a significant role [1,2,3], whereas ocular allergy is a hypersensitivity reaction against widespread antigens known as allergens. The pathologies are different, antigen presentation is a key mechanism in the inflammation that develops in both diseases [4,5,6]. Antigen-presenting cells (APCs) with their ability to take up, process, and present antigens, in association with MHC II-molecules, play a key role in immunological defense and tolerance mechanisms. The conjunctiva presents immunological similarities with other mucosal tissues, and organized lymphoid follicles can be found as conjunctiva-associated lymphoid follicles (CALT) [7,8]. Non-invasive in vivo two-photon microscopy revealed dynamic cellular processes and the ability to transport particles within the follicles [11]

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