Computational Analysis of Clinical and Molecular Markers and New Theranostic Possibilities in Primary Open-Angle Glaucoma

Abstract

Primary open-angle glaucoma (POAG) is a paramount cause of irreversible visual disability worldwide. We focus on identifying clinical and molecular facts that may help elucidating the pathogenic mechanisms of the disease. By using ophthalmological approaches (biomicroscopy, ocular fundus, optical coherence tomography, and perimetry) and experimental tests (enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), and Western blot/immunoblotting) directed to evaluate the oxidative stress, inflammation, apoptosis, and neurodegeneration processes, we gather information to build a network of data to perform a computational bioinformatics analysis. Our results showed strong interaction of the above players and its downstream effectors in POAG pathogenesis. In conclusion, specific risk factors were identified, and molecules involved in multiple pathways were found in relation to anterior and posterior eye segment glaucoma changes, pointing to new theranostic challenges for better managing POAG progression.

miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks

“…We also found the miR-26b-5p in tears of our GPAA patients and OHT individuals. Oxidative/nitrosative stress plays a pivotal role in POAG pathogenesis [ 12 , 15 , 39 ]; we may hypothesize that in the course of glaucoma, the pro-oxidants may induce the expression of miR-26b-5p, as reflected in this work [ 39 , 40 , 41 ]. Interestingly, hsa-miR-26b-5p has recently been involved in pseudoexfoliative glaucoma through interaction with the TGFR1 and TGR2 part of SMAD2 [ 42 ].…”

“…Oxidative stress, inflammation, and apoptosis are relevant mechanisms involved in POAG [ 3 , 4 , 5 , 6 , 7 , 8 , 12 , 15 , 39 ]. In this regard, oxidative stress can trigger a wide spectrum of transcription factors such as p53, Nrf2, NF-κB, AP-1, PPAR-γ, and β-catenin/Wnt, among others [ 57 , 58 , 59 , 60 ].…”

“…Despite great advances in glaucoma, there is still no reliable biomarker that can pre-clinically identify subjects at risk of POAG initiation and progression. Molecular-genetic diagnostic challenges for POAG are needed to complete the current knowledge in disease pathogenesis as well as to design new diagnostic and therapeutic strategies gathered under the recently proposed term glaucoma theranostics [ 15 ] for better eye care.…”

Clinical Tear Fluid Proteomics—A Novel Tool in Glaucoma Research

“…In future studies, more can be achieved when tear proteomics is combined with information obtained from other sample materials as well as extensive clinical and lifestyle information. A recent study by Pinazo-Durán et al [ 108 ] implemented computational analysis on a large collection of data originating from various imaging tools as well as enzyme linked immunosorbent assay (ELISA), LC, and Western blots. These types of analyses, which combine data from various sources, are likely to enable the discovery of the underlying biological pathways and associated molecules, which are most likely numerous in a multifactorial disease such as glaucoma.…”