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

Hu, Lin; Yang, Hongxia; Ai, Ming; Jiang, Shaoliang

doi:10.1007/s00417-017-3772-0

Cited by 43 publications

(34 citation statements)

References 52 publications

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“…Studies revealed that TLR4 is involved in the activity of late endothelial progenitor cells (32) and was upregulated in the retina of DR rats and in HRECs cultured in HG (33). The TLR4/NF-κB signaling pathway was activated in retinal ganglion cells under high glucose and TLR4 inhibition suppressed HG-induced apoptosis (34). Consist with previous studies, the activation of TLR4/NF-κB pathway was observed with the treatment of HG in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 63%

Gastrodin inhibits high glucose‑induced human retinal endothelial cell apoptosis by regulating the SIRT1/TLR4/NF‑κBp65 signaling pathway

et al. 2018

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Diabetic retinopathy (DR), one of the most common complications of late‑phase diabetes, is associated with the ectopic apoptosis of microvascular cells. Gastrodin, a phenolic glucoside derived from Gastrodia elata Blume, has been reported to have antioxidant and anti‑inflammation activities. The aim of the present study was to investigate the effects of gastrodin on high glucose (HG)‑induced human retinal endothelial cell (HREC) injury and its underlying mechanism. The results demonstrated that HG induced cell apoptosis in HRECs, which was accompanied by increased levels of reactive oxygen species production. Gastrodin treatment significantly alleviated HG‑induced apoptosis and oxidative stress. Furthermore, HG stimulation decreased the levels of SIRT1, which was accompanied by an increase in Toll‑like receptor 4 (TLR4) expression and the levels of phosphorylated nuclear factor (NF)‑κBp65. However, the administration of gastrodin significantly inhibited the activation of the sirtuin 1 (SIRT1)/TLR4/NF‑κBp65 signaling pathway in HRECs exposed to HG. Collectively, the present study demonstrated that gastrodin may be effective against HG‑induced apoptosis and its action may be exerted through the regulation of the SIRT1/TLR4/NF‑κBp65 signaling pathway.

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Section: Discussionsupporting

confidence: 63%

Gastrodin inhibits high glucose‑induced human retinal endothelial cell apoptosis by regulating the SIRT1/TLR4/NF‑κBp65 signaling pathway

et al. 2018

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“…Toll-like receptor 4 (TLR4) is a type of pattern recognition receptor, and is involved in innate and adaptive immunity by producing pro-inflammation cytokines, chemokines and apoptosis [9] . Studies have reported that TLR4 in the central nervous system (CNS) involved in memory, learning impairment [10] and cognitive decline [11].…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

et al. 2020

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Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that β2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4-KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups: (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.

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“…Retinal ganglion cells (RGCs) are output neurons which relay visual signals from the retina to the brain visual centers. Mice RGCs treated with 5 mM fructose upregulated NLRP1 expression after 24 h [109], while rat RGCs stimulated with 20 mM glucose for 48 h upregulated NLRP3 expression [127]. Inhibition of TLR4 using TAK-242 was found to attenuate NLRP3 and IL-1β production in the rat RGCs [127].…”

Section: Nlrs In Diabetic Retinopathymentioning

confidence: 95%

“…Mice RGCs treated with 5 mM fructose upregulated NLRP1 expression after 24 h [109], while rat RGCs stimulated with 20 mM glucose for 48 h upregulated NLRP3 expression [127]. Inhibition of TLR4 using TAK-242 was found to attenuate NLRP3 and IL-1β production in the rat RGCs [127]. Retinal microvascular endothelial cells form the crucial inner BRB that shields the inner retina from circulatory insult.…”

Section: Nlrs In Diabetic Retinopathymentioning

confidence: 98%

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

Lim

Wieser

Ganga

et al. 2020

IJMS

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Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression. The recent surge in literature associated with NOD-like receptors (NLRs) has gained massive attraction due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, a central phenomenon found in the pathogenesis of ocular diseases including DR. The NLR family of receptors are expressed in different eye tissues during pathological conditions suggesting their potential roles in dry eye, ocular infection, retinal ischemia, cataract, glaucoma, age-related macular degeneration (AMD), diabetic macular edema (DME) and DR. Our group is interested in studying the critical early components involved in the immune cell infiltration and inflammatory pathways involved in the progression of DR. Recently, we reported that NLRP3 inflammasome might play a pivotal role in the pathogenesis of DR. This comprehensive review summarizes the findings of NLRs expression in the ocular tissues with special emphasis on its presence in the retinal microglia and DR pathogenesis.

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

Abstract: 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.

Cited by 43 publications

References 52 publications

Gastrodin inhibits high glucose‑induced human retinal endothelial cell apoptosis by regulating the SIRT1/TLR4/NF‑κBp65 signaling pathway

Gastrodin inhibits high glucose‑induced human retinal endothelial cell apoptosis by regulating the SIRT1/TLR4/NF‑κBp65 signaling pathway

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

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