ArticleMolecular therapy. Nucleic acids2017
Adeno-Associated Viral Vector-Mediated mTOR Inhibition by Short Hairpin RNA Suppresses Laser-Induced Choroidal Neovascularization.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- mTOR downregulation promotes anti-inflammatory responses via the CCL3-CCR5 axis in hypoxic retinopathy.Molecular therapy. Methods & clinical development · 2025Article
- AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Review
- GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target.Cells · 2022Review
- mTOR Signalling Pathway: A Potential Therapeutic Target for Ocular Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- TGF-β promotes pericyte-myofibroblast transition in subretinal fibrosis through the Smad2/3 and Akt/mTOR pathways.Experimental & molecular medicine · 2022Article
- Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation.Acta pharmaceutica Sinica. B · 2022Article
- Role of mTORC1 activity during early retinal development and lamination in human-induced pluripotent stem cell-derived retinal organoids.Cell death discovery · 2022Article
- AAV expressing an mTOR-inhibiting siRNA exhibits therapeutic potential in retinal vascular disorders by preserving endothelial integrity.FEBS open bio · 2022Article
- Article
- The mTOR/NF-κB Pathway Mediates Neuroinflammation and Synaptic Plasticity in Diabetic Encephalopathy.Molecular neurobiology · 2021Article
- Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye.Pharmaceutics · 2021Review
- A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals.International journal of molecular sciences · 2020Review
- Inhibition of mTOR via an AAV-Delivered shRNA Tested in a Rat OIR Model as a Potential Antiangiogenic Gene Therapy.Investigative ophthalmology & visual science · 2020Article
- Transduction Pattern of AAVs in the Trabecular Meshwork and Anterior-Segment Structures in a Rat Model of Ocular Hypertension.Molecular therapy. Methods & clinical development · 2019Article
- Effects of Stuffer DNA on the Suppression of Choroidal Neovascularization by a rAAV Expressing a mTOR-Inhibiting shRNA.Molecular therapy. Methods & clinical development · 2019Article
- Essential Role of mTOR Signaling in Human Retinal Pigment Epithelial Cell Regeneration After Laser Photocoagulation.Lasers in medical science · 2019Article
- mTORC1 and mTORC2 are differentially engaged in the development of laser-induced CNV.Cell communication and signaling : CCS · 2019Article
- Adeno-Associated Viral Vector 2 and 9 Transduction Is Enhanced in Streptozotocin-Induced Diabetic Mouse Retina.Molecular therapy. Methods & clinical development · 2019Article
- Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model.Molecular therapy. Methods & clinical development · 2018Article
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9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Choroidal neovascularization (CNV) is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD) and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF), the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR) has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA), which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV. Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA) after generating CNV lesions in the eyes via laser photocoagulation. The recombinant adeno-associated virus (rAAV) delivery vehicle was able to effectively transduce cells in the inner retina, and significantly fewer inflammatory cells and less extensive CNV were observed in the animals treated with rAAV-mTOR shRNA when compared with control- and rAAV-scrambled shRNA-treated groups. Presumably related to the reduction of CNV, increased autophagy was detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer apoptotic cells detected in the outer nuclear layer around the CNV indicate that mTOR inhibition may also have neuroprotective effects. Taken together, these results demonstrate the therapeutic potential of mTOR inhibition, resulting from rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV.
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