Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies
Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and the most widely used model for ischemic retinopathies, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). OIR model has been used to test new potential...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00873/full |
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| author | Maria Vähätupa Tero A. H. Järvinen Tero A. H. Järvinen Hannele Uusitalo-Järvinen Hannele Uusitalo-Järvinen |
| author_facet | Maria Vähätupa Tero A. H. Järvinen Tero A. H. Järvinen Hannele Uusitalo-Järvinen Hannele Uusitalo-Järvinen |
| author_sort | Maria Vähätupa |
| collection | DOAJ |
| description | Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and the most widely used model for ischemic retinopathies, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). OIR model has been used to test new potential anti-angiogenic factors for human diseases. We have recently performed the most comprehensive characterization of OIR by a relatively novel mass spectrometry (MS) technique, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS) proteomics and used genetically modified mice strains to identify novel molecular drug targets in angiogenic retinal diseases. We have confirmed the relevance of the identified molecular targets to human diseases by determining their expression pattern in neovascular membranes obtained from PDR and RVO patients. Based on our results, crystallins were the most prominent proteins induced by early hypoxic environment during the OIR, while actomyosin complex and Filamin A-R-Ras axis, that regulates vascular permeability of the angiogenic blood vessels, stood out at the peak of angiogenesis. Our results have revealed potential new therapeutic targets to address hypoxia-induced pathological angiogenesis and the associated vascular permeability in number of retinal diseases. |
| first_indexed | 2024-04-14T00:45:08Z |
| format | Article |
| id | doaj.art-5f76bb517ac3403397a5e9d7085293f7 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T00:45:08Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5f76bb517ac3403397a5e9d7085293f72022-12-22T02:22:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-06-011110.3389/fphar.2020.00873516661Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in RetinopathiesMaria Vähätupa0Tero A. H. Järvinen1Tero A. H. Järvinen2Hannele Uusitalo-Järvinen3Hannele Uusitalo-Järvinen4Faculty of Medicine and Health Technology, Tampere University, Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandDepartment of Orthopedics and Traumatology, Tampere University Hospital, Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandEye Centre, Tampere University Hospital, Tampere, FinlandOxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and the most widely used model for ischemic retinopathies, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). OIR model has been used to test new potential anti-angiogenic factors for human diseases. We have recently performed the most comprehensive characterization of OIR by a relatively novel mass spectrometry (MS) technique, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS) proteomics and used genetically modified mice strains to identify novel molecular drug targets in angiogenic retinal diseases. We have confirmed the relevance of the identified molecular targets to human diseases by determining their expression pattern in neovascular membranes obtained from PDR and RVO patients. Based on our results, crystallins were the most prominent proteins induced by early hypoxic environment during the OIR, while actomyosin complex and Filamin A-R-Ras axis, that regulates vascular permeability of the angiogenic blood vessels, stood out at the peak of angiogenesis. Our results have revealed potential new therapeutic targets to address hypoxia-induced pathological angiogenesis and the associated vascular permeability in number of retinal diseases.https://www.frontiersin.org/article/10.3389/fphar.2020.00873/fullhypoxiaangiogenesisvascular permeabilityR-Rasfilaminmyosin |
| spellingShingle | Maria Vähätupa Tero A. H. Järvinen Tero A. H. Järvinen Hannele Uusitalo-Järvinen Hannele Uusitalo-Järvinen Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies Frontiers in Pharmacology hypoxia angiogenesis vascular permeability R-Ras filamin myosin |
| title | Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies |
| title_full | Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies |
| title_fullStr | Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies |
| title_full_unstemmed | Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies |
| title_short | Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies |
| title_sort | exploration of oxygen induced retinopathy model to discover new therapeutic drug targets in retinopathies |
| topic | hypoxia angiogenesis vascular permeability R-Ras filamin myosin |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00873/full |
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