Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation
Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/7/1557 |
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| author | Jorge González-Zamora María Hernandez Sergio Recalde Jaione Bezunartea Ana Montoliu Valentina Bilbao-Malavé Josune Orbe José A. Rodríguez Sara Llorente-González Patricia Fernández-Robredo Alfredo García-Layana |
| author_facet | Jorge González-Zamora María Hernandez Sergio Recalde Jaione Bezunartea Ana Montoliu Valentina Bilbao-Malavé Josune Orbe José A. Rodríguez Sara Llorente-González Patricia Fernández-Robredo Alfredo García-Layana |
| author_sort | Jorge González-Zamora |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10<sup>-/-</sup> mice developed smaller laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target. |
| first_indexed | 2024-03-09T03:40:19Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T03:40:19Z |
| publishDate | 2022-06-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-4fbdbf57ed3a4eb0bc822cc34f1dfa1d2023-12-03T14:41:33ZengMDPI AGBiomedicines2227-90592022-06-01107155710.3390/biomedicines10071557Matrix Metalloproteinase 10 Contributes to Choroidal NeovascularisationJorge González-Zamora0María Hernandez1Sergio Recalde2Jaione Bezunartea3Ana Montoliu4Valentina Bilbao-Malavé5Josune Orbe6José A. Rodríguez7Sara Llorente-González8Patricia Fernández-Robredo9Alfredo García-Layana10Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainNavarra Institute for Health Research, IdiSNA, 31008 Pamplona, SpainNavarra Institute for Health Research, IdiSNA, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, SpainAge-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10<sup>-/-</sup> mice developed smaller laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.https://www.mdpi.com/2227-9059/10/7/1557matrix metalloproteinaseage-related macular degenerationoxidative stresschoroidal neovascularisationangiogenesis |
| spellingShingle | Jorge González-Zamora María Hernandez Sergio Recalde Jaione Bezunartea Ana Montoliu Valentina Bilbao-Malavé Josune Orbe José A. Rodríguez Sara Llorente-González Patricia Fernández-Robredo Alfredo García-Layana Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation Biomedicines matrix metalloproteinase age-related macular degeneration oxidative stress choroidal neovascularisation angiogenesis |
| title | Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation |
| title_full | Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation |
| title_fullStr | Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation |
| title_full_unstemmed | Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation |
| title_short | Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation |
| title_sort | matrix metalloproteinase 10 contributes to choroidal neovascularisation |
| topic | matrix metalloproteinase age-related macular degeneration oxidative stress choroidal neovascularisation angiogenesis |
| url | https://www.mdpi.com/2227-9059/10/7/1557 |
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