ArticleNature communications2024
The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- FASN mediates crosstalk between autophagy and lipid metabolism via the AMPK-MTOR pathway in early age-related macular degeneration.Autophagy · 2026Article
- Research Progress on the Pathogenesis and Diagnostic and Therapeutic Potential of Ciliopathies Regulated by IFT172.Clinical genetics · 2026Review
- Restoration of impaired lysosomal function mitigates drusen-like deposit formation and cell death in Malattia Leventinese.JCI insight · 2026Article
- An siRNA targetingMolecular therapy. Nucleic acids · 2026Article
- STING activation induces polarized cytokine secretion of IFN-β and IL-17A promoting photoreceptor death and choroidal disruption in age-related macular degeneration.Cell death & disease · 2026Article
- Role and regulation of kinases in age-related macular degeneration.Journal of translational medicine · 2026Review
- Dysregulated Polarized Secretion of Small Extracellular Vesicles in the Retinal Pigment Epithelium: Mechanisms and Pathological Roles in Age-Related Macular Degeneration.Journal of inflammation research · 2026Review
- Divergent ocular safety profiles of glucagon-like peptide-1 receptor agonists: a pharmacological heterogeneity framework.Frontiers in medicine · 2026Review
- AI driven 3D subcellular RPE map discovers cell state transitions in establishment of apical-basal polarity.NPJ artificial intelligence · 2026Article
- Trained immunity attenuated acute lung injury by activating alveolar macrophages via AKT2-PDK1 axis-mediated metabolic reprogramming.Journal of translational medicine · 2025Article
- C5a-Induced Autophagy Dysfunction Promotes Choroidal Neovascularization Through the ROS-Inflammatory Pathway.Investigative ophthalmology & visual science · 2025Article
- Molecular Determinants of the Human Retinal Pigment Epithelium Cell Fate and Potential Pharmacogenomic Targets for Precision Medicine.International journal of molecular sciences · 2025Article
- Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice.Aging cell · 2025Article
- Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2025Review
- Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration.Cellular & molecular biology letters · 2025Review
- iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.Stem cells translational medicine · 2025Review
- Naringin Suppresses CoClAntioxidants (Basel, Switzerland) · 2025Article
- How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.Experimental eye research · 2025Review
- The AMD-associated genetic polymorphism CFH Y402H confers vulnerability to Hydroquinone-induced stress in iPSC-RPE cells.Frontiers in immunology · 2025Article
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Authors and funding
34 authors.
Funding
Abstract
Non-neovascular or dry age-related macular degeneration (AMD) is a multi-factorial disease with degeneration of the aging retinal-pigmented epithelium (RPE). Lysosomes play a crucial role in RPE health via phagocytosis and autophagy, which are regulated by transcription factor EB/E3 (TFEB/E3). Here, we find that increased AKT2 inhibits PGC-1α to downregulate SIRT5, which we identify as an AKT2 binding partner. Crosstalk between SIRT5 and AKT2 facilitates TFEB-dependent lysosomal function in the RPE. AKT2/SIRT5/TFEB pathway inhibition in the RPE induced lysosome/autophagy signaling abnormalities, disrupted mitochondrial function and induced release of debris contributing to drusen. Accordingly, AKT2 overexpression in the RPE caused a dry AMD-like phenotype in aging Akt2 KI mice, as evident from decline in retinal function. Importantly, we show that induced pluripotent stem cell-derived RPE encoding the major risk variant associated with AMD (complement factor H; CFH Y402H) express increased AKT2, impairing TFEB/TFE3-dependent lysosomal function. Collectively, these findings suggest that targeting the AKT2/SIRT5/TFEB pathway may be an effective therapy to delay the progression of dry AMD.
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