Fig. 7: Schematic plot of DDR2 enhancing ferroptosis sensitivity via the Src-Hippo pathway in highly myopic cataract. | Cell Death & Disease

Fig. 7: Schematic plot of DDR2 enhancing ferroptosis sensitivity via the Src-Hippo pathway in highly myopic cataract.

From: Enhanced ferroptosis sensitivity promotes the formation of highly myopic cataract via the DDR2-Hippo pathway

Fig. 7

In highly myopic eyes, the elevated levels of TGF-β1 in the lens microenvironment contribute to an increased expression of DDR2. This, in turn, activates the Src kinase, which promotes the nuclear translocation of key effectors of the Hippo pathway: YAP1 and its homolog WWTR1. YAP1 upregulates the transcription of ACSL4 and TfR1, while simultaneously downregulating GPX4 at the post-translational level, which collectively enhance the lens’s sensitivity to ferroptosis, manifesting as increased levels of Fe2+, lipid peroxidation, and mitochondrial distortion. Ultimately, the heightened ferroptosis sensitivity accelerates the formation of nuclear cataracts in highly myopic lenses.

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