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

Abstract

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.

Keywords: allergic conjunctivitis; biomarker; keratoconus; ocular allergy; proteome.

Figure 1

Allergy biopathway from immunoglobulin E (IgE) production for a specific allergen, to signs and symptoms of ocular allergy experienced upon re-exposure. These include itchiness, redness, swelling, irritation and inflammation of the ocular surface and surrounding tissues.

Figure 2

In order to collect human tear samples using the microcapillary flow technique, participants were asked to sit facing forward with their heads tilted all the way to one side to ensure basal tears from the surface of the eye pooled in the lateral canthus (outer corner of the eye). With sterile, gloved hands, glass microcapillary tubes were used to draw tears from the ocular surface. Following sample collection, proteome analysis is typically conducted using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), automated electrophoretic technology (AET) or mass spectrometry techniques (in order of increasing accuracy).

Figure 3

Comparison of differentially expressed proteins in patients with keratoconus and ocular allergy, and proteins that are altered in either condition [3,21,40,47,48,50,51,52,53,54,55,56,57]. Ocular allergy and keratoconus have been linked in recent research through ocular surface changes caused by increased eye-rubbing experienced by sufferers of both conditions. Protein expression on the ocular surface in both conditions has been studied recently, as overlapping key proteins appear to be affected similarly. ^† MMP—matrix metalloproteinase.