Mechanical-biochemical signaling accelerates scleral remodeling in myopia via the LaminA/C-Emerin-MKL1 axis

However, the mechanism underlying the onset and progression of scleral remodeling remains unclear. Here, based on reanalysis of single-cell RNA sequencing data, we showed that aberrant biomechanics in the sclera serve as signals that promote extracellular matrix (ECM) remodeling during the development of myopia via LaminA/C-Emerin-MKL1 axis, and followed by a decrease in collagen synthesis in scleral fibroblasts.

Mice with lens-induced myopia (LIM) and guinea pigs with form-deprivation myopia (FDM) exhibited nuclear deformation and dysregulation of nuclear envelope (NE) proteins in sclera. We established a mechanical model to investigate the role of matrix stiffness in regulating collagen synthesis in human primary scleral fibroblasts. In contrast to stiff substrates, soft matrix attenuated the sequestration of LaminA/C and Emerin in the NE and impaired MKL1 nuclear accumulation and COL1A1 transcription.