1. Academic Validation
  2. Enhancement of lens extraction-induced MCP-1 upregulation and microglia response in long-term diabetes via c-jun, stat1 and ERK

Enhancement of lens extraction-induced MCP-1 upregulation and microglia response in long-term diabetes via c-jun, stat1 and ERK

  • Life Sci. 2020 Nov 15;261:118360. doi: 10.1016/j.lfs.2020.118360.
Yizhen Tang 1 Houfa Yin 2 Wei Wang 2 Xiaobo Zhang 2 Naibin Chu 2 Su Li 2 Chenxi Yan 2 Qiuli Fu 2 Ke Yao 3
Affiliations

Affiliations

  • 1 Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
  • 2 Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
  • 3 Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address: xlren@zju.edu.cn.
Abstract

Aim: Diabetic patients are reported to have a higher incidence of cataract surgery-induced retinal complications, possibly due to retinal inflammation. Our goal is to identify the key inflammatory cytokines, cells and regulatory pathways involved.

Main methods: Diabetes mellitus (DM) induced by streptozotocin and control mice received extracapsular lens extraction (ECLE) in one eye. Neuroretinas were collected at postoperative day1(P1), day2(P2), and day7(P7). BV2 cells were harvested under the treatment of high glucose, lipopolysaccharide (LPS) and inhibitors. The method of qPCR, western blot and immunohistochemistry were used to identify the expression of cytokines and signaling pathways.

Key findings: ECLE induced increased inflammation in the neuroretina of surgery eye with a peak at P1. MCP-1 surge in long-term diabetes mellitus (LDM) mice at P1 is higher than short-term diabetes mellitus (SDM) mice and normal mice. Significant activation of c-jun and c-fos were found in LDM compared to normal and SDM. Advanced activation of STAT1 and ERK was found at P1 in LDM instead of at P2 in SDM and Normal. Activation of microglia/macrophage was also detected in the LDM mice. Besides the inhibition of c-jun/JNK, MCP-1 expression can be attenuated by inhibiting STAT1 and ERK under high glucose condition after LPS stimulation.

Significance: Enhancement of lens extraction-induced MCP-1 upregulation and microglia response in long-term diabetes might be due to the activation of cjun, STAT1 and ERK, which provided potential therapeutic targets to attenuate retinal inflammation after surgery in diabetic individuals.

Keywords

Cataract surgery; Diabetes mellitus; MCP-1.

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