title: Toll-like receptor 4 in bone marrow-derived cells contributes to the progression of diabetic retinopathy.
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.
authors.affiliation: The Department of Medical Genetics, Tongji Medical College Affiliated with Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430022, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Radiology Department, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China.
authors.forename: Haojun
authors.identifier: 0000-0002-2512-5403
authors.initials: H
authors.lastname: Shi
authors.affiliation: The Department of Ophthalmology, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China ; The Department of Ophthalmology, No. 1 Hospital of Xian City, 30 Powder Lane, South Street, Xi'an, Shanxi 710002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, NW607 MUH, 3459 Fifth Avenue, Pittsburgh, PA 25213, USA.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Wang
authors.affiliation: The Department of Emergency Surgery, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Department of Ophthalmology, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China.
authors.forename: Fagang
authors.initials: F
authors.lastname: Jiang
authors.affiliation: The Department of Ophthalmology, Union Hospital Affiliated with Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D012160:Retina / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A