Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients

Frontiers in Medicine

Medicine

Julian García–Feijoo¹  Carolina García–Villanueva²  Jorge Vila-Arteaga³  Alex Gallego–Martínez⁴  Irene Andrés–Blasco⁵  Maria D. Pinazo-Durán⁵  Jose J. García-Medina⁶  Carlo Nucci⁷  Alessio Martucci⁷  Vicente Zanón-Moreno⁸  Cristina Peris-Martínez⁹ 

[1] Department of Ophthalmology, The University Clinic Hospital “San Carlos”, Madrid, Spain;Department of Ophthalmology, The University General Hospital, Valencia, Spain;Department of Ophthalmology, University and Polytechnic Hospital “La Fe”, Valencia, Spain;Ophthalmic Research Unit “Santiago Grisolia”, Foundation for Research in Health and Biomedicine (FISABIO), Valencia, Spain;Cellular and Molecular Ophthalmobiology Group, Surgery Department, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain;Ophthalmic Research Unit “Santiago Grisolia”, Foundation for Research in Health and Biomedicine (FISABIO), Valencia, Spain;Cellular and Molecular Ophthalmobiology Group, Surgery Department, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain;Spanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, Spain;Ophthalmic Research Unit “Santiago Grisolia”, Foundation for Research in Health and Biomedicine (FISABIO), Valencia, Spain;Spanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, Spain;Department of Ophthalmology, The General University Hospital “Morales Meseguer”, Murcia, Spain;Department of Ophthalmology and Optometry, University of Murcia, Murcia, Spain;Ophthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy;Spanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, Spain;Biosanitary Research Institute, Valencian International University (VIU), Valencia, Spain;Spanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, Spain;Medical Ophthalmology FISABIO-FOM Center, Valencia, Spain;

关键词: primary open-angle glaucoma;    glaucoma neurodegeneration;    biomarkers;    molecules;    genes;    miRNAs;   

DOI  :  10.3389/fmed.2023.1157773

 received in 2023-02-03, accepted in 2023-04-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionGlaucoma is a chronic neurodegenerative disease, which is the leading cause of irreversible blindness worldwide. As a response to high intraocular pressure, the clinical and molecular glaucoma biomarkers indicate the biological state of the visual system. Classical and uncovering novel biomarkers of glaucoma development and progression, follow-up, and monitoring the response to treatment are key objectives to improve vision outcomes. While the glaucoma imaging field has successfully validated biomarkers of disease progression, there is still a considerable need for developing new biomarkers of early glaucoma, that is, at the preclinical and initial glaucoma stages. Outstanding clinical trials and animal-model study designs, innovative technology, and analytical approaches in bioinformatics are essential tools to successfully uncover novel glaucoma biomarkers with a high potential for translation into clinical practice.MethodsTo better understand the clinical and biochemical-molecular-genetic glaucoma pathogenesis, we conducted an analytical, observational, and case-comparative/control study in 358 primary open-angle glaucoma (POAG) patients and 226 comparative-control individuals (CG) to collect tears, aqueous humor, and blood samples to be processed for identifying POAG biomarkers by exploring several biological pathways, such as inflammation, neurotransmitter/neurotrophin alteration, oxidative stress, gene expression, miRNAs fingerprint and its biological targets, and vascular endothelial dysfunction, Statistics were done by using the IBM SPSS 25.0 program. Differences were considered statistically significant when p ≤ 0.05.ResultsMean age of the POAG patients was 70.03 ± 9.23 years, and 70.62 ± 7.89 years in the CG. Malondialdehyde (MDA), nitric oxide (NO), interleuquin (IL)-6, endothelin-1 (ET-1), and 5 hydroxyindolacetic acid (5-HIAA), displayed significantly higher levels in the POAG patients vs. the CG (p < 0.001). Total antioxidant capacity (TAC), brain derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), solute carrier family 23-nucleobase transporters-member 2 (SLC23A2) gene, and the glutathione peroxidase 4 (GPX4) gene, showed significantly lower levelsin the POAG patients than in the CG (p < 0.001). The miRNAs that differentially expressed in tear samples of the POAG patients respect to the CG were the hsa miR-26b-5p (involved in cell proliferation and apoptosis), hsa miR-152-3p (regulator of cell proliferation, and extracellular matrix expression), hsa miR-30e-5p (regulator of autophagy and apoptosis), and hsa miR-151a-3p (regulator of myoblast proliferation).DiscussionWe are incredibly enthusiastic gathering as much information as possible on POAG biomarkers to learn how the above information can be used to better steer the diagnosis and therapy of glaucoma to prevent blindness in the predictable future. In fact, we may suggest that the design and development of blended biomarkers is a more appropriate solution in ophthalmological practice for early diagnosis and to predict therapeutic response in the POAG patients.

【 授权许可】

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Copyright © 2023 Pinazo-Durán, Zanón-Moreno, García–Villanueva, Martucci, Peris-Martínez, Vila-Arteaga, García-Medina, Andrés–Blasco, Gallego–Martínez, Nucci and García–Feijoo.