What's the situation with ocular inflammation? A cross-seasonal investigation of proteomic changes in ocular allergy sufferers' tears in Victoria, Australia.

Background: Ocular allergy (OA) is a localized subset of allergy characterized by ocular surface itchiness, redness and inflammation. Inflammation and eye-rubbing, due to allergy-associated itch, are common in OA sufferers and may trigger changes to the ocular surface biochemistry. The primary aim of this study is to assess the differences in the human tear proteome between OA sufferers and Healthy Controls (HCs) across peak allergy season and off-peak season in Victoria, Australia. Methods: 19 participants (14 OA sufferers, 5 HCs) aged 18-45 were recruited for this study. Participants were grouped based on allergy symptom assessment questionnaire scoring. Proteins were extracted from human tear samples and were run on an Orbitrap Mass Spectrometer. Peaks were matched to a DIA library. Data was analyzed using the software MaxQuant, Perseus and IBM SPSS. Results: 1267 proteins were identified in tear samples of OA sufferers and HCs. 23 proteins were differentially expressed between peak allergy season OA suffers vs HCs, and 21 were differentially expressed in off-peak season. Decreased proteins in OA sufferers related to cell structure regulation, inflammatory regulation and antimicrobial regulation. In both seasons, OA sufferers were shown to have increased expression of proteins relating to inflammation, immune responses and cellular development. Conclusion: Tear protein identification showed dysregulation of proteins involved in inflammation, immunity and cellular structures. Proteins relating to cellular structure may suggest a possible link between OA-associated itch and the subsequent ocular surface damage via eye-rubbing, while inflammatory and immune protein changes highlight potential diagnostic and therapeutic biomarkers of OA.

The Plight of the Metabolite: Oxidative Stress and Tear Film Destabilisation Evident in Ocular Allergy Sufferers across Seasons in Victoria, Australia.

Ocular allergy (OA) is characterised by ocular surface itchiness, redness, and inflammation in response to allergen exposure. The primary aim of this study was to assess differences in the human tear metabolome and lipidome between OA and healthy controls (HCs) across peak allergy (spring-summer) and off-peak (autumn-winter) seasons in Victoria, Australia. A total of 19 participants (14 OA, 5 HCs) aged 18-45 were recruited and grouped by allergy questionnaire score. Metabolites and lipids from tear samples were analysed using mass spectrometry. Data were analysed using TraceFinder and Metaboanalyst. Metabolomics analysis showed 12 differentially expressed (DE) metabolites between those with OA and the HCs during the peak allergy season, and 24 DE metabolites were found in the off-peak season. The expression of niacinamide was upregulated in OA sufferers vs. HCs across both seasons (p ≤ 0.05). A total of 6 DE lipids were DE between those with OA and the HCs during the peak season, and 24 were DE in the off-peak season. Dysregulated metabolites affected oxidative stress, inflammation, and homeostasis across seasons, suggesting a link between OA-associated itch and ocular surface damage via eye rubbing. Tear lipidome changes were minimal between but suggested tear film destabilisation and thinning. Such metabolipodome findings may pave new and exciting ways for effective diagnostics and therapeutics for OA sufferers in the future.

A Review of Emerging Tear Proteomics Research on the Ocular Surface in Ocular Allergy.

Ocular allergy is an immunoglobulin E-mediated Type I hypersensitivity reaction localised to the ocular surface and surrounding tissues. Primary signs and symptoms of ocular allergy include itching, redness, irritation and inflammation. Eye-rubbing caused by itching has been shown to alter ocular surface protein concentrations in conditions linked to ocular allergy such as keratoconus. In keratoconus, the cornea begins to thin and sag over time, leading to progressive vision loss and blindness in severe conditions. Due to the high incidence of ocular allergy sufferers rubbing their eyes in response to symptoms of itching, the protein landscape of the ocular surface may be significantly altered. Differential protein expression caused by long-term inflammation and eye-rubbing may lead to subsequent changes in ocular surface structure and function over time. This review aims to summarise and explore the findings of current ocular allergy proteome research conducted using techniques such as gel electrophoresis, mass spectrometry and lab-on-a-chip proteomics. Proteins of interest for this review include differentially expressed immunoglobulins, mucins, functional proteins, enzymes and proteins with previously uncharacterised roles in ocular allergy. Additionally, potential applications of this research are addressed in terms of diagnostics, drug development and future research prospects.

To See or Not to See: A Systematic Review of the Importance of Human Ocular Surface Cytokine Biosignatures in Ocular Allergy.

Cytokines are key cell signalling proteins in a number of immune and homeostatic pathways of the human body. In particular, they mediate intracellular mechanisms of allergy on the ocular surface by triggering cellular responses that result in typical physiological ocular allergy symptoms, such as itchiness, watery eyes, irritation, and swelling. Given the recent research focus in optometry on the aetiology of corneal ectasia subtypes like keratoconus, there is an increasing need for the development of new clinical diagnostic methods. An increasing trend is evident among recent publications in cytokine studies, whereby the concentrations of cytokines in healthy and disease states are compared to derive a specific cytokine profile for that disease referred to as 'biosignatures'. Biosignatures have diagnostic applications in ocular allergy as a cheap, non-invasive alternative to current techniques like IgE antibody testing and skin prick tests. Cytokine detection from tear samples collected via microcapillary flow can be analysed either by enzyme-linked immunosorbent assays (ELISA), multiplex magnetic bead assays, or immunoblot assays. Characterising patient hypersensitivities through diagnostic tests is the first step to managing exposure to triggers. Investigating cytokine biosignatures in ocular allergy and their links to physiology are imperative and will be the focus of this systematic review article.