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.

Abstract

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.

• Authors: Xue Cai, Sudipta Seal, James F McGinnis
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 1 Pg. 249-58 (Jan 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24140045 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• NF-kappa B
• Receptors, LDL
• VLDL receptor
• Cerium
• ceric oxide
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinase 5

Topics

• Animals
• Cerium (administration & dosage, pharmacology)
• Gene Expression Regulation
• MAP Kinase Kinase Kinase 5 (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-kappa B (metabolism)
• Nanoparticles
• Neovascularization, Pathologic
• Oxidative Stress
• Polymerase Chain Reaction
• Receptors, LDL (genetics, physiology)
• Vitreous Body
• p38 Mitogen-Activated Protein Kinases (metabolism)