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Mediators of Inflammation
Volume 2014, Article ID 858763, 7 pages
http://dx.doi.org/10.1155/2014/858763
Research Article

Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy

1The Department of Medical Genetics, Tongji Medical College Affiliated with Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430022, China
2Radiology Department, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China
3The Department of Ophthalmology, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China
4The Department of Ophthalmology, No. 1 Hospital of Xian City, 30 Powder Lane, South Street, Xi’an, Shanxi 710002, China
5Department of Surgery, University of Pittsburgh Medical Center, NW607 MUH, 3459 Fifth Avenue, Pittsburgh, PA 25213, USA
6The Department of Emergency Surgery, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China

Received 11 February 2014; Revised 25 June 2014; Accepted 24 July 2014; Published 17 August 2014

Academic Editor: Eeva Moilanen

Copyright © 2014 Hui Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetic retinopathy (DR) is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4) plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM) induction by streptozotocin (STZ) treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α). Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1β, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR.