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AAV expressing an mTOR‐inhibiting siRNA exhibits therapeutic potential in retinal vascular disorders by preserving endothelial integrity

Expanding on previous demonstrations of the therapeutic effects of adeno‐associated virus (AAV) carrying small‐hairpin RNA (shRNA) in downregulating the mechanistic target of rapamycin (mTOR) in in vivo retinal vascular disorders, vascular endothelial growth factor (VEGF)‐stimulated endothelial cell...

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Detalles Bibliográficos
Autores principales: Cha, Seho, Seo, Won‐il, Woo, Ha‐Na, Kim, Hee Jong, Lee, Steven Hyun Seung, Kim, Jin, Choi, Jun‐Sub, Park, Keerang, Lee, Joo Yong, Lee, Beom Jun, Lee, Heuiran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727948/
https://www.ncbi.nlm.nih.gov/pubmed/34431239
http://dx.doi.org/10.1002/2211-5463.13281
Descripción
Sumario:Expanding on previous demonstrations of the therapeutic effects of adeno‐associated virus (AAV) carrying small‐hairpin RNA (shRNA) in downregulating the mechanistic target of rapamycin (mTOR) in in vivo retinal vascular disorders, vascular endothelial growth factor (VEGF)‐stimulated endothelial cells were treated with AAV2‐shmTOR to examine the role of mTOR inhibition in retinal angiogenesis. AAV2‐shmTOR exposure significantly reduced mTOR expression in human umbilical vein endothelial cells (HUVECs) and decreased downstream signaling cascades of mTOR complex 1 (mTORC1) and mTORC2 under VEGF treatment. Moreover, the angiogenic potential of VEGF was significantly inhibited by AAV2‐shmTOR, which preserved endothelial integrity by maintaining tight junctions between HUVECs. These data thus support previous in vivo studies and provide evidence that AAV2‐shmTOR induces therapeutic effects by inhibiting the neovascularization of endothelial cells.