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

ABSTRACT: Scleral remodeling is the pathological basis of axial elongation during the progression of myopia. 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. Interventions for MKL1 induced or inhibited the progression of myopia in vivo. We illustrate the therapeutic potential of a novel mechanointerference strategy that blocks scleral remodeling and myopia progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE316874 | GEO | 2026/06/03

REPOSITORIES: GEO

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