Sustained inhibition of neovascularization in vldlr^{鈭?鈭?/span>} mice following intravitreal injection of cerium oxide nanoparticles and the role of the ASK1-P38/JNK-NF-魏B pathway

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• 作者：Xue Cai ; Sudipta Seal ; James F. McGinnis
• 关键词：Nanoceria ; vldlr&minus ; /&minus ; mouse ; Neovascularization ; Retinal degeneration ; Signal transduction
• 刊名：Biomaterials
• 出版年：January, 2014
• 年：2014
• 卷：35
• 期：1
• 页码：249-258
• 全文大小：3462 K

文摘

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^鈭?鈭?/em>) 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^{鈭?鈭?/sup> 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-魏B signaling pathway by nanoceria was investigated. Our data demonstrated that a single intravitreal injection of nanoceria in P28 vldlr鈭?鈭?/em> 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-魏B signaling pathway.}