Sustained inhibition of neovascularization in vldlr-/- mice following intravitreal injection of cerium oxide nanoparticles and the role of the ASK1-P38/JNK-NF-κB pathway.
Sustained inhibition of neovascularization in vldlr-/- mice following intravitreal injection of cerium oxide nanoparticles and the role of the ASK1-P38/JNK-NF-κB pathway.
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DOI：
10.1016/j.biomaterials.2013.10.022
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发表时间：
2014-01
期刊：
影响因子：
14
通讯作者：
McGinnis, James F.
中科院分区：
文献类型：
--
作者：
Cai, Xue;Seal, Sudipta;McGinnis, James F.
氧化铈纳米颗粒（nanoceria）是直接的抗氧化剂;它们在单次玻璃体内注射到新生极低密度脂蛋白受体敲除（vldlr−/−）小鼠后抑制病理性新生血管形成。然而，纳米氧化铈对眼部现有病理性新生血管消退的长期治疗效果和机制尚不清楚。我们玻璃体内注射P28 vldlr−/−小鼠，并将分析终点延长至P70。数据表明，纳米氧化铈维持其治疗功能长达6周。纳米铈作用的多个参数进行了检查，包括：现有的异常血管的回归，减少血管渗漏，下调血管内皮生长因子（VEGF），丙烯醛，胶质细胞酸性蛋白（GFAP）和半胱天冬酶3的表达，以及上调视杆细胞和视锥细胞视蛋白基因的表达。研究纳米氧化铈对ASK 1-P38/JNK-NF-κB信号通路的调节作用。我们的数据表明，在P28 vldlr−/−小鼠中单次玻璃体内注射纳米氧化铈可使现有氧化应激诱导的新生血管形成持续消退，防止血管渗漏，并通过下调ASK 1-P38/JNK-NF-κB信号通路抑制细胞凋亡。
Cerium oxide nanoparticles (nanoceria) are direct antioxidants; they inhibit pathological neovascularization following a single intravitreal injection into new born very low density lipoprotein receptor knockout (vldlr−/−) mice. However, the long-term therapeutic effects and mechanisms of nanoceria action on regression of the existing pathologic neovascularization in the eyes are unknown. We intravitreally injected P28 vldlr−/− mice and extended the endpoint for analysis until P70. The data demonstrate that nanoceria sustained their therapeutic function up to 6 weeks. Multiple parameters for nanoceria effects were examined including: regression of existing abnormal blood vessels, reduction of vascular leakage, down-regulation of the expression of vascular endothelial growth factor (VEGF), acrolein, glial fibrillary acidic protein (GFAP) and caspase 3 as well as up-regulation of the expression of rod- and cone-opsin genes. Regulation of ASK1-P38/JNK-NF-κB signaling pathway by nanoceria was investigated. Our data demonstrated that a single intravitreal injection of nanoceria in P28 vldlr−/− mice produced sustained regression of existing oxidative stress-induced neovascularizations, prevented blood vessel leakage and inhibited apoptosis via down-regulation of the ASK1-P38/JNK-NF-κB signaling pathway.
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影响因子：
14
作者：
Das S;Singh S;Dowding JM;Oommen S;Kumar A;Sayle TX;Saraf S;Patra CR;Vlahakis NE;Sayle DC;Self WT;Seal S
通讯作者：
Seal S
影响因子：
6.1
作者：
Kong, Li;Cai, Xue;Zhou, Xiaohong;Wong, Lily L.;Karakoti, Ajay S.;Seal, Sudipta;McGinnis, James F.
通讯作者：
McGinnis, James F.
影响因子：
15
作者：
Karakoti, Ajay S.;Singh, Sanjay;Kumar, Amit;Malinska, Maura;Kuchibhatla, Satyanarayana V. N. T.;Wozniak, Krzysztof;Self, William T.;Seal, Sudipta
通讯作者：
Seal, Sudipta
影响因子：
3.1
作者：
Chen Y;Hu Y;Moiseyev G;Zhou KK;Chen D;Ma JX
通讯作者：
Ma JX
影响因子：
5.6
作者：
Dong, Aling;Xie, Bing;Shen, Jikui;Yoshida, Tsunehiko;Yokoi, Katsutoshi;Hackett, Sean F.;Campochiaro, Peter A.
通讯作者：
Campochiaro, Peter A.