Matrix stiffness modulate the mitochondrial function and ferroptosis of retinal pigment epithelia cells

Meng-Ling Chiang¹, Rong-Shing Chang¹, Chi-Shuo Chen^1*

¹Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan

* Presenter:Chi-Shuo Chen, email:chen.chishuo@gmail.com

Age-related macular degeneration (AMD) is a leading cause of vision loss in adults, and it is estimated that nearly 300 million people will be affected by AMD by the year 2040. Drusen deposition on the retinal pigment epithelial (RPE) cells and changes in retinal stiffness are critical pathological features of AMD, and our preliminary bioinformatic analysis reveal a strong correlation between cell adhesion and polarity with AMD. However, the physiological impact of mechanical signaling on RPE is not fully elucidated. Herein, our preliminary in vitro experiments suggest a connection between the mechanical properties of the microenvironment and RPE ferroptosis. Moreover, the alteration of substrate stiffness modulates the mitochondrial function and intracellular iron accumulation. Higher intracellular oxidative stress elicited hyperphosphorylation of PI3K/Akt, ERK1/2, JNK, p38 MAPK, and p65 NF-κB in ARPE-19 cells. By understanding the cell mechanics and their regulatory role in RPE, this project is expected to provide further insights into the pathological basis of AMD and its potential application in AMD treatment.

Keywords: cell mechanics, age-related macular degeneration, ferroptosis