Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models
Abstract Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly population. Anti-vascular endothelial growth factor (VEGF) antibody therapy is applicable to neovascularisation of AMD; however, the prevention of fibrosis after anti-VEGF monotherapy is an unmet medical n...
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-18531-y |
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| author | Eunhye Yu Yunjeong Song Sun Mi Gu Yang Hee Jo Sang Won Yeon Kyu Jin Han Mi Kyeong Lee Jung Kee Min Jaesuk Yun |
| author_facet | Eunhye Yu Yunjeong Song Sun Mi Gu Yang Hee Jo Sang Won Yeon Kyu Jin Han Mi Kyeong Lee Jung Kee Min Jaesuk Yun |
| author_sort | Eunhye Yu |
| collection | DOAJ |
| description | Abstract Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly population. Anti-vascular endothelial growth factor (VEGF) antibody therapy is applicable to neovascularisation of AMD; however, the prevention of fibrosis after anti-VEGF monotherapy is an unmet medical need. Subretinal fibrosis causes vision loss in neovascular age-related macular degeneration (nAMD) even with anti-VEGF therapy. We report the anti-fibrotic and anti-neovascularisation effects of alpinumisoflavone (AIF), an isoflavonoid derived from unripe Maclura tricuspidata fruit, in in vitro and in vivo models. For in vitro study, we treated H2O2 or THP-1 conditioned media (TCM) following activation with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) in a human retinal pigment epithelial cell line (ARPE-19). Choroidal neovascularisation (CNV) was induced by laser photocoagulation in mice, immediately followed by intravitreal administration of 25 μg AIF. CNV area and fibrosis were measured 7 days after laser photocoagulation. AIF showed anti-fibrosis and anti-neovascularisation effects in both the models. The laser induced CNV area was reduced upon AIF administration in nAMD mouse model. Additionally, AIF decreased the levels of the cleaved form of crystallin alpha B (CRYAB), a chaperone associated with VEGF stabilisation and fibrosis. Our results demonstrate a novel therapeutic application of AIF against neovascularisation and fibrosis in nAMD. |
| first_indexed | 2024-04-13T01:41:34Z |
| format | Article |
| id | doaj.art-0a98b216220c4097828dd256f26eea15 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T01:41:34Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0a98b216220c4097828dd256f26eea152022-12-22T03:08:09ZengNature PortfolioScientific Reports2045-23222022-08-0112111210.1038/s41598-022-18531-yAlpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo modelsEunhye Yu0Yunjeong Song1Sun Mi Gu2Yang Hee Jo3Sang Won Yeon4Kyu Jin Han5Mi Kyeong Lee6Jung Kee Min7Jaesuk Yun8College of Pharmacy, Chungbuk National UniversityCollege of Pharmacy, Chungbuk National UniversityCollege of Pharmacy, Chungbuk National UniversityCollege of Pharmacy, Chungbuk National UniversityCollege of Pharmacy, Chungbuk National UniversityDepartment of Ophthalmology, Ulsan University Hospital, University of Ulsan, College of MedicineCollege of Pharmacy, Chungbuk National UniversityCollege of Pharmacy, Chungbuk National UniversityCollege of Pharmacy, Chungbuk National UniversityAbstract Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly population. Anti-vascular endothelial growth factor (VEGF) antibody therapy is applicable to neovascularisation of AMD; however, the prevention of fibrosis after anti-VEGF monotherapy is an unmet medical need. Subretinal fibrosis causes vision loss in neovascular age-related macular degeneration (nAMD) even with anti-VEGF therapy. We report the anti-fibrotic and anti-neovascularisation effects of alpinumisoflavone (AIF), an isoflavonoid derived from unripe Maclura tricuspidata fruit, in in vitro and in vivo models. For in vitro study, we treated H2O2 or THP-1 conditioned media (TCM) following activation with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) in a human retinal pigment epithelial cell line (ARPE-19). Choroidal neovascularisation (CNV) was induced by laser photocoagulation in mice, immediately followed by intravitreal administration of 25 μg AIF. CNV area and fibrosis were measured 7 days after laser photocoagulation. AIF showed anti-fibrosis and anti-neovascularisation effects in both the models. The laser induced CNV area was reduced upon AIF administration in nAMD mouse model. Additionally, AIF decreased the levels of the cleaved form of crystallin alpha B (CRYAB), a chaperone associated with VEGF stabilisation and fibrosis. Our results demonstrate a novel therapeutic application of AIF against neovascularisation and fibrosis in nAMD.https://doi.org/10.1038/s41598-022-18531-y |
| spellingShingle | Eunhye Yu Yunjeong Song Sun Mi Gu Yang Hee Jo Sang Won Yeon Kyu Jin Han Mi Kyeong Lee Jung Kee Min Jaesuk Yun Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models Scientific Reports |
| title | Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models |
| title_full | Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models |
| title_fullStr | Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models |
| title_full_unstemmed | Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models |
| title_short | Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models |
| title_sort | alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age related macular degeneration in in vitro and in vivo models |
| url | https://doi.org/10.1038/s41598-022-18531-y |
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