Dysfunctional Nurr1 promotes high glucose-induced Müller cell activation by up-regulating the NF-κB/NLRP3...

Area of Science:

• Ophthalmology
• Endocrinology
• Molecular Biology

Background:

• Diabetic retinopathy (DR) is a leading cause of vision loss in diabetes mellitus (DM).
• Müller cell dysfunction, induced by high glucose, exacerbates DR pathogenesis.
• Nuclear receptor subfamily 4 group A member 2 (Nurr1) is known to suppress inflammatory pathways.

Purpose of the Study:

• To investigate the role of Nurr1 in Müller cells during DR.
• To determine if Nurr1 dysfunction promotes the NF-κB/NLRP3 inflammasome axis in DR.
• To evaluate Nurr1 as a potential therapeutic target for DR.

Main Methods:

• In vitro studies using Müller cells exposed to high glucose.
• Assessing Nurr1 expression, nuclear translocation, and NF-κB/NLRP3 inflammasome activation.
• In vivo studies using a streptozotocin-induced diabetic mouse model treated with a Nurr1 agonist (C-DIM12).

Main Results:

• High glucose reduced Nurr1 expression and nuclear translocation in Müller cells.
• NF-κB (p65) activation and NLRP3 inflammasome upregulation were observed.
• Treatment with the Nurr1 agonist C-DIM12 reduced retinal ganglion cell loss in diabetic mice.

Conclusions:

• Nurr1 exhibits anti-inflammatory and neuroprotective effects in Müller cells during DR.
• Nurr1 dysfunction contributes to DR pathogenesis via the NF-κB/NLRP3 inflammasome pathway.
• Nurr1 represents a promising molecular target for DR treatment.