Activation of Toll-like receptor 3 promotes pathological corneal neovascularization by enhancement of SDF-1-mediated endothelial progenitor cell recruitment.

Abstract

Toll-like receptors (TLRs) play an important role in inflammatory and immunological responses, which are intimately related to neovascularization. However, the precise mode of action of TLR3 in neovascularization still remains ambiguous. In this study, we sought to investigate the role of TLR3 in pathological corneal neovascularization (CNV) using a mouse model of alkali-induced CNV. CNV was attenuated in TLR3-deficient mice, and the absence of TLR3 led to decreased production of stromal cell-derived factor 1 (SDF-1), a well-characterized cytokine that regulates the recruitment of endothelial progenitor cells (EPCs) to the sites of neo-angiogenic niches in the injured tissues. Topical administration of polyinosinic-polycytidylic acid [poly (I:C)], a synthetic ligand for TLR3, to the injured cornea promoted CNV in wild type (WT) mice but not in TLR3-deficient mice. In addition, the effect of poly (I:C) on WT mice was abolished by addition of SDF-1 receptor antagonist AMD 3100. Furthermore, poly (I:C) treatment in vitro enhanced the migration of EPCs, whereas the enhanced migration was abolished by AMD 3100. These results indicate an essential role of TLR3 signalling in CNV that involves upregulating SDF-1 production and recruiting EPCs to the sites of injury for neovascularization. Thus, targeting the TLR3 signalling cascade may constitute a novel therapeutic approach for treating neovascularization-related diseases.

• Authors: Ruijuan Zhao, Jing Zhang, Yan Wang, Jiayi Jin, Hongyan Zhou, Jianping Chen, Shao Bo Su
• Journal: Experimental eye research (Exp Eye Res) Vol. 178 Pg. 177-185 (01 2019) ISSN: 1096-0007 [Electronic] England
• PMID: 30321512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Chemokine CXCL12
• Cxcl12 protein, mouse
• TLR3 protein, mouse
• Toll-Like Receptor 3
• Sodium Hydroxide
• Poly I-C

Topics

• Administration, Ophthalmic
• Animals
• Burns, Chemical (metabolism)
• Cell Movement (physiology)
• Chemokine CXCL12 (metabolism)
• Cornea (drug effects)
• Corneal Neovascularization (chemically induced, metabolism, pathology)
• Disease Models, Animal
• Endothelial Progenitor Cells (cytology)
• Eye Burns (chemically induced)
• Fluorescent Antibody Technique, Indirect
• Mice
• Mice, Inbred C57BL
• Poly I-C (pharmacology)
• Real-Time Polymerase Chain Reaction
• Signal Transduction (physiology)
• Sodium Hydroxide (toxicity)
• Toll-Like Receptor 3 (metabolism)