Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice

Tears are a complex biological mixture containing electrolytes, metabolites, lipids, mucins, some small organic molecules, and proteins. The tear film has various roles in the lubrication, protection from the external environment, and nutrition of the cornea; it is also involved in the modulation of the optical properties of the eye. Tear composition reflects the physiological condition of the underlying tissues. Therefore, the tear fluid is useful in the evaluation of health and disease states and it is a valuable source of biomarkers for objective analysis of ocular and systemic diseases. The relatively high protein concentration of this fluid and the ease of noninvasive sample collection make it suitable for diagnostic and prognostic purposes. Efforts in proteomics research have positively affected to the field of ophthalmology, and the knowledge on the tear proteome has expanded considerably in the last few years. Nevertheless, despite a large amount of available data and the many biomarkers proposed for several eye and systemic diseases, the extent of translation to well-characterized and clinically useful tools has been largely insufficient. As for most of other biofluids, the road from discovery to clinical application is still long and full of pitfalls. In this review, we discuss the proteomic approaches used in the characterization of tear protein and peptide content, recapitulating the main studies and the progress done. We also present a brief summary of the path from discovery to clinical application of tear protein markers, with some representative examples of translation from the bench to the bedside. Significance In this review we cover the most relevant proteomic approaches used in the characterization of the tear proteome, and for the first time we also focus in advances performed in the nowadays emerging peptide content characterization. In this context, we recapitulate on the main studies and the progresses done in this field. We also present a concise overview of the course that may be happen from discovery to clinical application for tear protein markers. Finally we include some representative examples of translation from the bench to the bedside.