Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately l...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/5/596 |
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| author | Ana S. Falcão Margarida L. Pedro Sandra Tenreiro Miguel C. Seabra |
| author_facet | Ana S. Falcão Margarida L. Pedro Sandra Tenreiro Miguel C. Seabra |
| author_sort | Ana S. Falcão |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately leads to RPE damage and AMD progression. AMD is a complex pathology, so multitarget treatments are required to act on different pathways, presenting several challenges. In this review, we discuss the current knowledge on the pathogenesis of this disease, focusing mainly on lysosomal dysfunction and OxS. Because transcription factors regulate homeostasis, the transcription factor EB (TFEB), which controls lysosomal function and biogenesis, and the nuclear factor erythroid 2-related factor 2 (NRF2), which manages OxS, have been proposed as promising targets for disease intervention. Finally, we discuss the interplay of these pathways for a potential synergistic effect on AMD-targeted therapies, as they could change the course of today’s available treatments for AMD. |
| format | Article |
| id | doaj-art-2ac07d192bb24ad39e7da40d94c4a4f2 |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-2ac07d192bb24ad39e7da40d94c4a4f22025-08-20T01:56:17ZengMDPI AGAntioxidants2076-39212025-05-0114559610.3390/antiox14050596Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular DegenerationAna S. Falcão0Margarida L. Pedro1Sandra Tenreiro2Miguel C. Seabra3iNOVA4Health, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, 1169-056 Lisboa, PortugaliNOVA4Health, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, 1169-056 Lisboa, PortugaliNOVA4Health, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, 1169-056 Lisboa, PortugaliNOVA4Health, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, 1169-056 Lisboa, PortugalAge-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately leads to RPE damage and AMD progression. AMD is a complex pathology, so multitarget treatments are required to act on different pathways, presenting several challenges. In this review, we discuss the current knowledge on the pathogenesis of this disease, focusing mainly on lysosomal dysfunction and OxS. Because transcription factors regulate homeostasis, the transcription factor EB (TFEB), which controls lysosomal function and biogenesis, and the nuclear factor erythroid 2-related factor 2 (NRF2), which manages OxS, have been proposed as promising targets for disease intervention. Finally, we discuss the interplay of these pathways for a potential synergistic effect on AMD-targeted therapies, as they could change the course of today’s available treatments for AMD.https://www.mdpi.com/2076-3921/14/5/596age-related macular degenerationlysosomal dysfunctionNRF2oxidative stressretinal pigment epitheliumTFEB/mTORC1 axis |
| spellingShingle | Ana S. Falcão Margarida L. Pedro Sandra Tenreiro Miguel C. Seabra Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration Antioxidants age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis |
| title | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_full | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_fullStr | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_full_unstemmed | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_short | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_sort | targeting lysosomal dysfunction and oxidative stress in age related macular degeneration |
| topic | age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis |
| url | https://www.mdpi.com/2076-3921/14/5/596 |
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