Omics Biomarkers in Ophthalmology

Abstract

''Omics'' refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes. We observe that genomic analyses were mainly successful in AMD research (almost half of the genomic heritability has been explained), whereas large parts of disease variability or risk remain unsolved in most of the other diseases. Other omics studies like transcriptomics, proteomics, and metabolomics provided additional candidate proteins and pathways for several eye diseases, although sample sizes in these studies were often very small and replication is lacking. In order to translate omics results into clinical biomarkers, larger sample sizes and validation across different cohorts would be essential. In conclusion, omicsbased studies are increasing in ophthalmology, and further application to the clinic might develop in the years to come. Integration of genomics with other type of omics data has the potential to improve the accuracy of predictive tests. Moreover, in the future, omics may lead to stratification of patients into subgroups based on molecular profiles, enabling the development of personalized treatments.

A Metabolomics Profiling of Glaucoma Points to Mitochondrial Dysfunction, Senescence, and Polyamines Deficiency

“…[5][6][7] Despite its promising statistical power to uncover new pathophysiologic biomarkers, metabolomics only rarely has been applied to POAG to date. 8,9 Indeed, this approach, combining multiple small-molecule analysis with mathematic modeling, can reveal the direct or indirect metabolic fingerprints of a disease. In comparison with other ''omics'' techniques, metabolomics produces profiles closer to the phenotype of the disease, integrating several other factors in addition to the genetic factors.…”

Role of the Complement System in Chronic Central Serous Chorioretinopathy

“…[12][13][14][15][16] Unbiased genome-wide association studies (GWAS) have identified hundreds of genomic loci implicated in complex diseases, such as age-related macular degeneration (AMD), myopia, and glaucoma. 17 Such approaches have shed light on the genetic architecture of these diseases; however, establishing functional links between identified loci and disease remains challenging. Besides having direct effects on protein function or structure, SNPs can also influence the expression of nearby (cis) or distal (trans) genes.…”

Snake-like Chromatin Cell Protein as an Indicator of Chronic Eye Rubbing in Patients with Keratoconus and Allergic Conjunctivitis

“…5 Therefore, it has been postulated as a multifactorial disease. 4,5,7,22,23 Multiple studies have revealed an association with certain genes; 22,24 however, it currently cannot be diagnosed based on genetic screening. 23,24 Eye rubbing has been postulated as a significant risk factor by several authors.…”

“…4,5,7,22,23 Multiple studies have revealed an association with certain genes; 22,24 however, it currently cannot be diagnosed based on genetic screening. 23,24 Eye rubbing has been postulated as a significant risk factor by several authors. 3,5,7,[25][26][27] However, few studies [8][9][10][11][12][13][14][15] have referred to eye rubbing as the cause of keratoconus; therefore, it has recently attracted attention.…”

“…33 However, it is difficult to prove that the mechanical stress induced by severe eye rubbing can cause structural changes to the cornea but not to the chromatin of conjunctival epithelial cells, which is altered by eye rubbing, contact lens use, and dry eye friction. 17,22,24 A limitation of our study was that SLC was evaluated based on epithelial conjunctival cells instead of corneal epithelial cells because SLC has been studied just in conjunctival cells. However, it is widely known that keratoconus eyes present not only alterations limited to the cornea but also tears, and that the conjunctiva expresses inflammatory alterations.…”