Kaempferol attenuates retinal ganglion cell death by suppressing NLRP1/NLRP3 inflammasomes and caspase-8 via JNK and NF-κB pathways in acute glaucoma

Autor: Xiaomin Wu, Tongmei Zheng, Xiuchun Wang, Yiwei Chen, Chao-bin Lin, Fujin Wu
Rok vydání: 2018
Předmět:
Retinal Ganglion Cells
0301 basic medicine
genetic structures
Cell Survival
Inflammasomes
Blotting
Western

Inflammation
Pharmacology
Real-Time Polymerase Chain Reaction
Caspase 8
Antioxidants
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
NLR Family
Pyrin Domain-Containing 3 Protein

medicine
Animals
Kaempferols
Intraocular Pressure
Adaptor Proteins
Signal Transducing

Retina
business.industry
NLRP1
JNK Mitogen-Activated Protein Kinases
NF-kappa B p50 Subunit
Glaucoma
NF-κB
eye diseases
Mice
Inbred C57BL

Disease Models
Animal

Ophthalmology
030104 developmental biology
medicine.anatomical_structure
Microscopy
Fluorescence

Retinal ganglion cell
chemistry
Reperfusion Injury
sense organs
Signal transduction
medicine.symptom
Apoptosis Regulatory Proteins
Kaempferol
business
030217 neurology & neurosurgery
Zdroj: Eye (Lond)
ISSN: 1476-5454
0950-222X
DOI: 10.1038/s41433-018-0318-6
Popis: Aims or purpose Glaucoma is the leading cause of vision loss and blindness in the world. Elucidating the pathogenesis of glaucoma and developing effective treatment should be the priority. Inflammation and oxidative stress play essential roles in glaucoma pathogeneisis. Kaempferol is a natural flavonol and has anti-inflammatory and anti-oxidative activities. In this study, we explored the potential effects of kaempferol on acute glaucoma. Methods We established the retinal ischemia-reperfusion (I/R) mice model and administrated kaempferol to I/R mice. We monitored the retina thickness change, retinal ganglion cell (RGC) death, caspase-8 and caspase-3 activation, NLRP1/NLRP3 inflammasomes activation, pro-inflammatory cytokines production, and activations of NF-κB and MAPKs signaling pathways. Results Kaempferol prevented retina thickness change and RGC death in I/R mice. The activations of caspase-8, caspase-3, and NLRP1/NLRP3 inflammasome activation were inhibited by kaempferol. Kaempferol prevented pro-inflammatory cytokines productions in I/R mice. The activation of NF-κB and JNK signaling pathways was also inhibited by Kaempferol in I/R mice. Conclusion Kaempferol attenuated retinal ganglion cell death by suppressing NLRP1/NLRP3 inflammasomes and caspase-8 via inhibiting NF-κB and JNK pathways in acute glaucoma.
Databáze: OpenAIRE