New Lipid Mediators in Retinal Angiogenesis and Retinopathy
Retinal diseases associated with vascular destabilization and the inappropriate proliferation of retinal endothelial cells have major consequences on the retinal vascular network. In extreme cases, the development of hypoxia, the upregulation of growth factors, and the hyper-proliferation of unstabl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00739/full |
| _version_ | 1811306031257485312 |
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| author | Ingrid Fleming Ingrid Fleming |
| author_facet | Ingrid Fleming Ingrid Fleming |
| author_sort | Ingrid Fleming |
| collection | DOAJ |
| description | Retinal diseases associated with vascular destabilization and the inappropriate proliferation of retinal endothelial cells have major consequences on the retinal vascular network. In extreme cases, the development of hypoxia, the upregulation of growth factors, and the hyper-proliferation of unstable capillaries can result in bleeding and vision loss. While anti-vascular endothelial growth factor therapy and laser retinal photocoagulation can be used to treat the symptoms of late stage disease, there is currently no treatment available that can prevent disease progression. Cytochrome P450 enzymes metabolize endogenous substrates (polyunsaturated fatty acids) to bioactive fatty acid epoxides that demonstrate biological activity with generally protective/anti-inflammatory and insulin-sensitizing effects. These epoxides are further metabolized by the soluble epoxide hydrolase (sEH) to fatty acid diols, high concentrations of which have vascular destabilizing effects. Recent studies have identified increased sEH expression and activity and the subsequent generation of the docosahexaenoic acid-derived diol; 19,20-dihydroxydocosapentaenoic acid, as playing a major role in the development of diabetic retinopathy. This review summarizes current understanding of the roles of cytochrome P450 enzyme and sEH–derived PUFA mediators in retinal disease. |
| first_indexed | 2024-04-13T08:37:03Z |
| format | Article |
| id | doaj.art-cb4a2cf4e5dc4ac3ac5ce4bcee9a9a32 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T08:37:03Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-cb4a2cf4e5dc4ac3ac5ce4bcee9a9a322022-12-22T02:54:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-07-011010.3389/fphar.2019.00739465956New Lipid Mediators in Retinal Angiogenesis and RetinopathyIngrid Fleming0Ingrid Fleming1Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe-University, Frankfurt, GermanyGerman Centre for Cardiovascular Research (DZHK) partner site RheinMain, Frankfurt, GermanyRetinal diseases associated with vascular destabilization and the inappropriate proliferation of retinal endothelial cells have major consequences on the retinal vascular network. In extreme cases, the development of hypoxia, the upregulation of growth factors, and the hyper-proliferation of unstable capillaries can result in bleeding and vision loss. While anti-vascular endothelial growth factor therapy and laser retinal photocoagulation can be used to treat the symptoms of late stage disease, there is currently no treatment available that can prevent disease progression. Cytochrome P450 enzymes metabolize endogenous substrates (polyunsaturated fatty acids) to bioactive fatty acid epoxides that demonstrate biological activity with generally protective/anti-inflammatory and insulin-sensitizing effects. These epoxides are further metabolized by the soluble epoxide hydrolase (sEH) to fatty acid diols, high concentrations of which have vascular destabilizing effects. Recent studies have identified increased sEH expression and activity and the subsequent generation of the docosahexaenoic acid-derived diol; 19,20-dihydroxydocosapentaenoic acid, as playing a major role in the development of diabetic retinopathy. This review summarizes current understanding of the roles of cytochrome P450 enzyme and sEH–derived PUFA mediators in retinal disease.https://www.frontiersin.org/article/10.3389/fphar.2019.00739/full19,20-dihydroxydocosapentaenoic acidcytochrome P450diabetic retinopathyepoxyeicosatrienoic acidsoluble epoxide hydrolase |
| spellingShingle | Ingrid Fleming Ingrid Fleming New Lipid Mediators in Retinal Angiogenesis and Retinopathy Frontiers in Pharmacology 19,20-dihydroxydocosapentaenoic acid cytochrome P450 diabetic retinopathy epoxyeicosatrienoic acid soluble epoxide hydrolase |
| title | New Lipid Mediators in Retinal Angiogenesis and Retinopathy |
| title_full | New Lipid Mediators in Retinal Angiogenesis and Retinopathy |
| title_fullStr | New Lipid Mediators in Retinal Angiogenesis and Retinopathy |
| title_full_unstemmed | New Lipid Mediators in Retinal Angiogenesis and Retinopathy |
| title_short | New Lipid Mediators in Retinal Angiogenesis and Retinopathy |
| title_sort | new lipid mediators in retinal angiogenesis and retinopathy |
| topic | 19,20-dihydroxydocosapentaenoic acid cytochrome P450 diabetic retinopathy epoxyeicosatrienoic acid soluble epoxide hydrolase |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00739/full |
| work_keys_str_mv | AT ingridfleming newlipidmediatorsinretinalangiogenesisandretinopathy AT ingridfleming newlipidmediatorsinretinalangiogenesisandretinopathy |