Extracellular-Matrix Mechanics Regulate the Ocular Physiological and Pathological Activities

Figure 3

Regulation of ECM stiffness in normal and pathological LC cells. Regulation of ECM stiffness in healthy and diseased LC cells. The diagram of a healthy LC cell in soft ECM (left) transforming into a pathological state (right) in a stiffer matrix. When ECM stiffness increases with aging or glaucoma, F-actin increases followed by YAP phosphorylation at tyrosine 357 elevates, while its serine 127 phosphorylation decreases, but the total YAP augments, resulting in elevated nuclear translocation and enhanced nuclear import (to some extent through direct F-actin-mediated pore opening) as well as lowered nuclear export, which correspondingly promotes the transcriptional activity of targets, leading to upregulation of ECM protein expression, enhanced myofibroblastic markers, incremental activation growth factors, and increased proliferation [72]. A “positive feedback loop” on the right illustrates how this cycle is self-sustaining. CTGF: connective tissue growth factor. α-SMA: α-smooth muscle actin. COLA1: α-1 type I collagen. c-myc: the regulator genes and proto-oncogenes that code for transcription factors.