Fig. 7: Proposed mechanism for TLR4/MD2 signaling and the effects of MD2 inhibitors on HOG-LDL-induced Müller cell dysfunction. | Experimental & Molecular Medicine

Fig. 7: Proposed mechanism for TLR4/MD2 signaling and the effects of MD2 inhibitors on HOG-LDL-induced Müller cell dysfunction.

From: MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4

Fig. 7

HOG-LDL activates TLR4 through MD2 in Müller cells. TLR4 activation is associated with the NOX4 and MyD88 interaction. The MyD88 pathway activates NF-κB to induce the expression of proinflammatory cytokines. However, the NOX4-TLR4 interaction increases ROS levels, leading to ER stress and mitochondrial dysfunction. Oxidative stress and unregulated inflammatory responses cause Müller cell apoptosis. Chalcone inhibitors of MD2 disrupt MD2-TLR4-NOX4 complex formation in HOG-LDL-challenged cells. The suppression of downstream oxidative stress and normalization of inflammatory responses prevent retinal Müller cell death.

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