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Resumo(s)
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.
Descrição
Funding Information: The authors acknowledge the support by the European COST Action CA20121: Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases (BenBedPhar). Webpage: https://benbedphar.org/about-benbedphar/ , accessed on 1 May 2025. Funding Information: Funded by \u201CLa Caixa\u2019 Foundation\u201D under the agreement HR22-00569 NASCENT and by the Research Unit UID/04462: iNOVA4Health\u2014Programa de Medicina Translacional and the Associated Laboratory LS4FUTURE (LA/P/0087/2020), both financially supported by Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia / Minist\u00E9rio da Educa\u00E7\u00E3o, Ci\u00EAncia e Inova\u00E7\u00E3o. Publisher Copyright: © 2025 by the authors.
Palavras-chave
age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology