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Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis.
Jing, Yutong; Zhao, Wanmin; Zhou, Ziyi; Wang, Wenzhe; Niu, Yali; He, Xiaoning; Chang, Tianfang; Guo, Changmei; Li, Bei; Dou, Guorui.
Afiliación
  • Jing Y; Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • Zhao W; State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi,
  • Zhou Z; State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi,
  • Wang W; Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • Niu Y; State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi,
  • He X; Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • Chang T; State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi,
  • Guo C; Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • Li B; Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • Dou G; State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi,
Adv Healthc Mater ; 13(17): e2303527, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38411334
ABSTRACT
Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Vesículas Extracelulares Límite: Animals / Humans Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Vesículas Extracelulares Límite: Animals / Humans Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania