1. Academic Validation
  2. Inhibition of TLR4 alleviates the inflammation and apoptosis of retinal ganglion cells in high glucose

Inhibition of TLR4 alleviates the inflammation and apoptosis of retinal ganglion cells in high glucose

  • Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2199-2210. doi: 10.1007/s00417-017-3772-0.
Lili Hu 1 Hongxia Yang 1 Ming Ai 2 Shuanghong Jiang 1
Affiliations

Affiliations

  • 1 Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang road, Wuchang district, Wuhan, Hubei, 430060, China.
  • 2 Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang road, Wuchang district, Wuhan, Hubei, 430060, China. lilyhbwh@163.com.
Abstract

Purpose: To investigate the expression profiles of Toll-like Receptor 4 (TLR4), the effect of TLR4 on inflammation, and Apoptosis of retinal ganglion cells (RGCs) cultured in high glucose and the underlying mechanism.

Methods: A high-glucose model was established in RGCs isolated from Sprague-Dawley (SD) rats (2-3 days old) and identified with Brn3a. Primary cultured RGCs were divided into control (0 mM), HG1 (10 mM glucose), HG2 (20 mM glucose), HG3 (30 mM glucose), HG (20 mM glucose) + TAK-242 (1.0 μM), and HG (20 mM glucose) + vehicle (1% DMSO) groups. The expression levels of TLR4, its downstream signalling molecules, and pro-inflammatory cytokines were measured by Real-Time PCR, Western blot or ELISA at 24 h and 48 h. The Apoptosis rate of RGCs was measured by flow cytometry.

Results: The mRNA and protein expression levels of TLR4 were increased in high-glucose groups (10 mM, 20 mM, 30 mM). Consistent with these findings, four TLR4 downstream signalling molecules (MyD88, NF-κB, TRAF6, NLRP3) and pro-inflammatory cytokines (IL-1β, IL-18) were upregulated in the three high-glucose groups. Apoptosis of RGCs was clearly increased in the high-glucose group. The administration of TAK-242, an antagonist of TLR4, inhibited inflammation and Apoptosis of RGCs in the high-glucose group.

Conclusion: Our results demonstrated that TLR4 plays a critical role in the inflammation and Apoptosis of RGCs induced by high glucose. TLR4 might become a novel potential pharmacological target for preventing the progression of DR.

Keywords

Toll-like receptor 4; apoptosis; diabetic retinopathy; inflammation; retinal ganglion cell.

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