Candidate Glaucoma Biomarkers: From Proteins to Metabolites, and the Pitfalls to Clinical Applications

Abstract

Glaucoma is an insidious group of eye diseases causing degeneration of the optic nerve, progressive loss of vision, and irreversible blindness. The number of people affected by glaucoma is estimated at 80 million in 2021, with 3.5% prevalence in people aged 40–80. The main biomarker and risk factor for the onset and progression of glaucoma is the elevation of intraocular pressure. However, when glaucoma is diagnosed, the level of retinal ganglion cell death usually amounts to 30–40%; hence, the urgent need for its early diagnosis. Molecular biomarkers of glaucoma, from proteins to metabolites, may be helpful as indicators of pathogenic processes observed during the disease’s onset. The discovery of human glaucoma biomarkers is hampered by major limitations, including whether medications are influencing the expression of molecules in bodily fluids, or whether tests to validate glaucoma biomarker candidates should include human subjects with different types and stages of the disease, as well as patients with other ocular and neurodegenerative diseases. Moreover, the proper selection of the biofluid or tissue, as well as the analytical platform, should be mandatory. In this review, we have summarized current knowledge concerning proteomics- and metabolomics-based glaucoma biomarkers, with specificity to human eye tissue and fluid, as well the analytical approach and the main results obtained. The complex data published to date, which include at least 458 different molecules altered in human glaucoma, merit a new, integrative approach allowing for future diagnostic tests based on the absolute quantification of local and/or systemic biomarkers of glaucoma.

Clinical Tear Fluid Proteomics—A Novel Tool in Glaucoma Research

“…In the genomics field, clinical researchers are trying to identify the genetic risk factors affecting glaucoma development [ 16 , 17 , 18 ]. In clinical proteomics, lipidomics, and metabolomics fields, the pathogenesis of glaucoma and its therapeutic options are being studied using various sample materials such as tear fluid, aqueous humor, vitreous body, and serum [ 19 , 20 , 21 ]. This review focuses specifically on how clinical tear proteomics is used to examine the development and treatment of glaucoma.…”

Based on multiple machine learning to identify the ENO2 as diagnosis biomarkers of glaucoma

“…Glaucoma is a group characterized by progressive degeneration of retinal ganglion cells of optic neuropathy, which is the main cause of blindness and raises the prevalence [ 1 , 2 ]. There are four categories of adult glaucoma: primary open-angle (POAG) and closed-angle glaucoma, and secondary open-angle (OAG) and closed-angle glaucoma (ACG).…”

“…Secondary glaucoma has some causes of elevated intraocular pressure, including trauma, neovascularization, pigment dispersion, inflammation or pseudodefoliation. The diagnosis and classification of glaucoma need to combine clinical examination, intraocular pressure measurement, visual field, and structural imaging parameters [ 2 , 3 ].…”

“…Studies have reported that small molecules to macromolecules, nucleic acids to proteins can be used as molecular biomarkers. At present, biomarkers in the tear film, aqueous humor, vitreous, and blood/serum have been proved to be useful in the diagnosis of glaucoma [ 2 ].…”

“…Previous studies have reported that hundreds of candidate biological markers have been proposed (> 450). However, biomarker diagnosis has not yet entered the clinical stage due to the sensitivity and specificity of the difference in the patient's genetic, sick and therapeutic phase [ 2 ]. Therefore, the candidate glaucoma biomarker will use to transform into clinical practice that still takes a lot of research.…”