Clinical Tear Fluid Proteomics—A Novel Tool in Glaucoma Research

Abstract

Tear fluid forms the outermost layer of the ocular surface and its characteristics and composition have been connected to various ocular surface diseases. As tear proteomics enables the non-invasive investigation of protein levels in the tear fluid, it has become an increasingly popular approach in ocular surface and systemic disease studies. Glaucoma, which is a set of multifactorial diseases affecting mainly the optic nerve and retinal ganglion cells, has also been studied using tear proteomics. In this condition, the complete set of pathophysiological changes occurring in the eye is not yet fully understood, and biomarkers for early diagnosis and accurate treatment selection are needed. More in-depth analyses of glaucoma tear proteomics have started to emerge only more recently with the implementation of LC-MS/MS and other modern technologies. The aim of this review was to examine the published data of the tear protein changes occurring during glaucoma, its topical treatment, and surgical interventions.

Tear nanoDSF Denaturation Profile Is Predictive of Glaucoma

“…Using in-gel trypsin digestion and MALDI-TOF peptide mass fingerprinting ( Figure 2 B), these proteins were recognized as lysozyme C (LYZ), lipocalin-1 (LCN1), serum albumin (HSA), lactotransferrin (LTF), and immunoglobulin kappa (light chain of IgA; IgA-κ), respectively. All of them were identified as core proteins of normal tear in previous proteomic studies [ 32 , 33 , 34 , 35 , 36 ] and recognized as potential TF biomarkers of POAG [ 12 ]. The quantitative analysis of the SDS-PAGE data elucidated a significant increase in HSA content, accompanied by a decrease in concentrations of LYZ, LCN1, and LTF in TF of POAG patients ( Figure 2 C,D).…”

“…TF represents a more convenient subject for analysis due to the simplicity and non-invasiveness of collection, and TF biomarkers of glaucoma have gained increasing attention over the last few years [ 12 , 13 ]. It was hypothesized that tears may become enriched in glaucoma-related molecules directly from the AH via scleral percolation in the uveoscleral pathway [ 14 ].…”

“…Growing evidence indicated that glaucomatous degeneration is indeed associated with characteristic alterations in TF components, such as soluble metabolites or lipids [ 9 , 16 , 17 ]. Furthermore, a number of promising biomarkers of glaucoma were revealed among TF proteins [ 12 ]. Some investigators suggest using single protein biomarkers of POAG, such as BDNF, matrix metallopeptidases, or cytokines [ 18 , 19 , 20 ].…”

Liquid Biopsy Proteomics in Ophthalmology

“…Collection of tear samples is a relatively simple and noninvasive procedure that does not require anesthesia . Tears can be collected using Schirmer’s strips, a glass microcapillary tube, or by a flush tear collection approach that instills ∼20–40 μL of 0.9% saline solution into the inferior palpebral fold of the eye. − Following sample collection, samples can be stored in a −80 °C freezer for several months (or years) before sample preparation.…”

Posttranslational modifications of proteins in diseased retina

“…Recent developments in proteomic research have made it possible to identify a set of proteins differentially posttranslationally modified in diseased retinas ( Garcia-Quintanilla et al, 2022 ; Lam et al, 2022 ; Lee et al, 2022 ; Nattinen et al, 2022 ; Smyczynska et al, 2022 ; Zhou H. et al, 2022 ). However, despite advancements in molecular knowledge regarding the retinal pathobiology of ocular diseases, the question of whether the differential expression of proteins associates with altered activity remains unaddressed.…”