Document Type
Article
Publication Date
2-23-2022
Abstract
Background The impairment of the inner blood–retinal barrier (iBRB) increases the pathological development of diabetic retinopathy (DR), a severe complication in diabetic patients. Identifying approaches to preserving iBRB integrity and function is a significant challenge in DR. C1q/tumor necrosis factor-related protein-3 (CTRP3) is a newly discovered adipokine and a vital biomarker, predicting DR severity. We sought to determine whether and how CTRP3 affects the pathological development of non-proliferative diabetic retinopathy (NPDR). Methods To clarify the pathophysiologic progress of the blood–retinal barrier in NPDR and explore its potential mechanism, a mouse Type 2 diabetic model of diabetic retinopathy was used. The capillary leakage was assessed by confocal microscope with fluorescent-labeled protein in vivo. Furthermore, the effect of CTRP3 on the inner blood–retinal barrier (iBRB) and its molecular mechanism was clarified. Results The results demonstrated that CTRP3 protects iBRB integrity and resists the vascular permeability induced by DR. Mechanistically, the administration of CTRP3 activates the AMPK signaling pathway and enhances the expression of Occludin and Claudin-5 (tight junction protein) in vivo and in vitro. Meanwhile, CTRP3 improves the injury of human retinal endothelial cells (HRMECs) induced by high glucose/high lipids (HG/HL), and its protective effects are AMPK-dependent. Conclusions In summary, we report, for the first time, that CTRP3 prevents diabetes-induced retinal vascular permeability via stabilizing the tight junctions of the iBRB and through the AMPK-dependent Occludin/Claudin-5 signaling pathway, thus critically affecting the development of NPDR.
Recommended Citation
Yan, Zheyi; Wang, Chunfang; Meng, Zhijun; Gan, Lu; Guo, Rui; Liu, Jing; Lau, Wayne Bond; Xie, Dina; Zhao, Jianli; Lopez, Bernard; Christopher, Theodore; Naik, Ulhas P.; Ma, Xin-Liang; and Wang, Yajing, "C1q/TNF-Related Protein 3 Prevents Diabetic Retinopathy via AMPK-Dependent Stabilization of Blood–Retinal Barrier Tight Junctions" (2022). Department of Medicine Faculty Papers. Paper 342.
https://jdc.jefferson.edu/medfp/342
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
Comments
This article is the author’s final published version in Cells, Volume 11, Issue 5, February 2022, Article number 779.
The published version is available at https://doi.org/10.3390/cells11050779. Copyright © Yan et al.
Publication made possible in part by support from the Jefferson Open Access Fund