Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration
Abstract Age-related macular degeneration (AMD) is an eye disease that can lead to legal blindness and vision loss. In its advanced stages, it is classified into dry and neovascular AMD. In neovascular AMD, the formation of new blood vessels disrupts the structure of the retina and induces an inflam...
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BMC
2025-04-01
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| Series: | Cellular & Molecular Biology Letters |
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| Online Access: | https://doi.org/10.1186/s11658-025-00732-8 |
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| author | Janusz Blasiak Elzbieta Pawlowska Hanna Helotera Maksim Ionov Marcin Derwich Kai Kaarniranta |
| author_facet | Janusz Blasiak Elzbieta Pawlowska Hanna Helotera Maksim Ionov Marcin Derwich Kai Kaarniranta |
| author_sort | Janusz Blasiak |
| collection | DOAJ |
| description | Abstract Age-related macular degeneration (AMD) is an eye disease that can lead to legal blindness and vision loss. In its advanced stages, it is classified into dry and neovascular AMD. In neovascular AMD, the formation of new blood vessels disrupts the structure of the retina and induces an inflammatory response. Treatment for neovascular AMD involves antibodies and fusion proteins targeting vascular endothelial growth factor A (VEGFA) and its receptors to inhibit neovascularization and slow vision loss. However, a fraction of patients with neovascular AMD do not respond to therapy. Many of these patients exhibit a subretinal fibrotic scar. Thus, retinal fibrosis may contribute to resistance against anti-VEGFA therapy and the cause of irreversible vision loss in neovascular AMD patients. Retinal pigment epithelium cells, choroidal fibroblasts, and retinal glial cells are crucial in the development of the fibrotic scar as they can undergo a mesenchymal transition mediated by transforming growth factor beta and other molecules, leading to their transdifferentiation into myofibroblasts, which are key players in subretinal fibrosis. Autophagy, a process that removes cellular debris and contributes to the pathogenesis of AMD, regardless of its type, may be stimulated by epithelial–mesenchymal transition and later inhibited. The mesenchymal transition of retinal cells and the dysfunction of the extracellular matrix—the two main aspects of fibrotic scar formation—are associated with impaired autophagy. Nonetheless, the causal relationship between autophagy and subretinal fibrosis remains unknown. This narrative/perspective review presents information on neovascular AMD, subretinal fibrosis, and autophagy, arguing that impaired autophagy may be significant for fibrosis-related resistance to anti-VEGFA therapy in neovascular AMD. Graphical Abstract |
| format | Article |
| id | doaj-art-50daae51e03947a6a322626e0eb24dc8 |
| institution | DOAJ |
| issn | 1689-1392 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj-art-50daae51e03947a6a322626e0eb24dc82025-08-20T02:55:31ZengBMCCellular & Molecular Biology Letters1689-13922025-04-0130112710.1186/s11658-025-00732-8Potential of autophagy in subretinal fibrosis in neovascular age-related macular degenerationJanusz Blasiak0Elzbieta Pawlowska1Hanna Helotera2Maksim Ionov3Marcin Derwich4Kai Kaarniranta5Faculty of Medicine, Collegium Medicum, Mazovian Academy in PlockDepartment of Pediatric Dentistry, Medical University of LodzDepartment of Ophthalmology, University of Eastern FinlandFaculty of Health Sciences, Mazovian Academy in PlockDepartment of Pediatric Dentistry, Medical University of LodzDepartment of Ophthalmology, University of Eastern FinlandAbstract Age-related macular degeneration (AMD) is an eye disease that can lead to legal blindness and vision loss. In its advanced stages, it is classified into dry and neovascular AMD. In neovascular AMD, the formation of new blood vessels disrupts the structure of the retina and induces an inflammatory response. Treatment for neovascular AMD involves antibodies and fusion proteins targeting vascular endothelial growth factor A (VEGFA) and its receptors to inhibit neovascularization and slow vision loss. However, a fraction of patients with neovascular AMD do not respond to therapy. Many of these patients exhibit a subretinal fibrotic scar. Thus, retinal fibrosis may contribute to resistance against anti-VEGFA therapy and the cause of irreversible vision loss in neovascular AMD patients. Retinal pigment epithelium cells, choroidal fibroblasts, and retinal glial cells are crucial in the development of the fibrotic scar as they can undergo a mesenchymal transition mediated by transforming growth factor beta and other molecules, leading to their transdifferentiation into myofibroblasts, which are key players in subretinal fibrosis. Autophagy, a process that removes cellular debris and contributes to the pathogenesis of AMD, regardless of its type, may be stimulated by epithelial–mesenchymal transition and later inhibited. The mesenchymal transition of retinal cells and the dysfunction of the extracellular matrix—the two main aspects of fibrotic scar formation—are associated with impaired autophagy. Nonetheless, the causal relationship between autophagy and subretinal fibrosis remains unknown. This narrative/perspective review presents information on neovascular AMD, subretinal fibrosis, and autophagy, arguing that impaired autophagy may be significant for fibrosis-related resistance to anti-VEGFA therapy in neovascular AMD. Graphical Abstracthttps://doi.org/10.1186/s11658-025-00732-8Neovascular age-related macular degenerationSubretinal fibrosisAutophagyEpithelial–mesenchymal transitionEndothelial–mesenchymal transitionTransforming growth factor beta 2 |
| spellingShingle | Janusz Blasiak Elzbieta Pawlowska Hanna Helotera Maksim Ionov Marcin Derwich Kai Kaarniranta Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration Cellular & Molecular Biology Letters Neovascular age-related macular degeneration Subretinal fibrosis Autophagy Epithelial–mesenchymal transition Endothelial–mesenchymal transition Transforming growth factor beta 2 |
| title | Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration |
| title_full | Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration |
| title_fullStr | Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration |
| title_full_unstemmed | Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration |
| title_short | Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration |
| title_sort | potential of autophagy in subretinal fibrosis in neovascular age related macular degeneration |
| topic | Neovascular age-related macular degeneration Subretinal fibrosis Autophagy Epithelial–mesenchymal transition Endothelial–mesenchymal transition Transforming growth factor beta 2 |
| url | https://doi.org/10.1186/s11658-025-00732-8 |
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