Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients
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 b...
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Frontiers Media S.A.
2023-05-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1157773/full |
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| author | Maria D. Pinazo-Durán Maria D. Pinazo-Durán Maria D. Pinazo-Durán Vicente Zanón-Moreno Vicente Zanón-Moreno Carolina García–Villanueva Alessio Martucci Cristina Peris-Martínez Cristina Peris-Martínez Jorge Vila-Arteaga Jose J. García-Medina Jose J. García-Medina Jose J. García-Medina Jose J. García-Medina Irene Andrés–Blasco Irene Andrés–Blasco Irene Andrés–Blasco Alex Gallego–Martínez Alex Gallego–Martínez Carlo Nucci Julian García–Feijoo |
| author_facet | Maria D. Pinazo-Durán Maria D. Pinazo-Durán Maria D. Pinazo-Durán Vicente Zanón-Moreno Vicente Zanón-Moreno Carolina García–Villanueva Alessio Martucci Cristina Peris-Martínez Cristina Peris-Martínez Jorge Vila-Arteaga Jose J. García-Medina Jose J. García-Medina Jose J. García-Medina Jose J. García-Medina Irene Andrés–Blasco Irene Andrés–Blasco Irene Andrés–Blasco Alex Gallego–Martínez Alex Gallego–Martínez Carlo Nucci Julian García–Feijoo |
| author_sort | Maria D. Pinazo-Durán |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T09:14:17Z |
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| language | English |
| last_indexed | 2024-03-13T09:14:17Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-8e47a5783e024b42b9e7ce208e62b91a2023-05-26T12:31:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-05-011010.3389/fmed.2023.11577731157773Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patientsMaria D. Pinazo-Durán0Maria D. Pinazo-Durán1Maria D. Pinazo-Durán2Vicente Zanón-Moreno3Vicente Zanón-Moreno4Carolina García–Villanueva5Alessio Martucci6Cristina Peris-Martínez7Cristina Peris-Martínez8Jorge Vila-Arteaga9Jose J. García-Medina10Jose J. García-Medina11Jose J. García-Medina12Jose J. García-Medina13Irene Andrés–Blasco14Irene Andrés–Blasco15Irene Andrés–Blasco16Alex Gallego–Martínez17Alex Gallego–Martínez18Carlo Nucci19Julian García–Feijoo20Ophthalmic Research Unit “Santiago Grisolia”, Foundation for Research in Health and Biomedicine (FISABIO), Valencia, SpainCellular and Molecular Ophthalmobiology Group, Surgery Department, Faculty of Medicine and Odontology, University of Valencia, Valencia, SpainSpanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, SpainSpanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, SpainBiosanitary Research Institute, Valencian International University (VIU), Valencia, SpainDepartment of Ophthalmology, The University General Hospital, Valencia, SpainOphthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, ItalySpanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, SpainMedical Ophthalmology FISABIO-FOM Center, Valencia, SpainDepartment of Ophthalmology, University and Polytechnic Hospital “La Fe”, Valencia, SpainOphthalmic Research Unit “Santiago Grisolia”, Foundation for Research in Health and Biomedicine (FISABIO), Valencia, SpainSpanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, SpainDepartment of Ophthalmology, The General University Hospital “Morales Meseguer”, Murcia, Spain0Department of Ophthalmology and Optometry, University of Murcia, Murcia, SpainOphthalmic Research Unit “Santiago Grisolia”, Foundation for Research in Health and Biomedicine (FISABIO), Valencia, SpainCellular and Molecular Ophthalmobiology Group, Surgery Department, Faculty of Medicine and Odontology, University of Valencia, Valencia, SpainSpanish Network of Inflammatory Diseases: REI-RICORS (RD21/0002/0032) of the Institute of Health Carlos III (ISCIII), Spanish Government, Madrid, SpainOphthalmic Research Unit “Santiago Grisolia”, Foundation for Research in Health and Biomedicine (FISABIO), Valencia, SpainCellular and Molecular Ophthalmobiology Group, Surgery Department, Faculty of Medicine and Odontology, University of Valencia, Valencia, SpainOphthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy1Department of Ophthalmology, The University Clinic Hospital “San Carlos”, Madrid, SpainIntroductionGlaucoma 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.https://www.frontiersin.org/articles/10.3389/fmed.2023.1157773/fullprimary open-angle glaucomaglaucoma neurodegenerationbiomarkersmoleculesgenesmiRNAs |
| spellingShingle | Maria D. Pinazo-Durán Maria D. Pinazo-Durán Maria D. Pinazo-Durán Vicente Zanón-Moreno Vicente Zanón-Moreno Carolina García–Villanueva Alessio Martucci Cristina Peris-Martínez Cristina Peris-Martínez Jorge Vila-Arteaga Jose J. García-Medina Jose J. García-Medina Jose J. García-Medina Jose J. García-Medina Irene Andrés–Blasco Irene Andrés–Blasco Irene Andrés–Blasco Alex Gallego–Martínez Alex Gallego–Martínez Carlo Nucci Julian García–Feijoo Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients Frontiers in Medicine primary open-angle glaucoma glaucoma neurodegeneration biomarkers molecules genes miRNAs |
| title | Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients |
| title_full | Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients |
| title_fullStr | Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients |
| title_full_unstemmed | Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients |
| title_short | Biochemical–molecular–genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients |
| title_sort | biochemical molecular genetic biomarkers in the tear film aqueous humor and blood of primary open angle glaucoma patients |
| topic | primary open-angle glaucoma glaucoma neurodegeneration biomarkers molecules genes miRNAs |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1157773/full |
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