CAMKMT knockdown delays myopia progression by reducing calcium Ion-mediated ER Stress-induced apoptosis.

Myopia, particularly high myopia, is a serious global public health issue. While CAMKMT is linked to axial length, its mechanistic role is unclear. In lens-induced myopic (LIM) guinea pigs, we performed intravitreal injection of shRNA CAMKMT-carrying AAV and measured ocular parameters. Non-invasive micro-test technology (NMT) revealed increased Ca2+ outflow in LIM sclera, exacerbating endoplasmic reticulum (ER) stress. Protein docking and Co-IP confirmed ERNI-HSPA5 interaction. LIM animals showed increased axial length, decreased refraction, and thinner sclera. Masson staining, western blot, and immunofluorescence indicated altered scleral remodeling; flow cytometry and TUNEL staining showed elevated apoptosis. Importantly, CAMKMT knockdown reduced ER stress, suppressed apoptosis, ameliorated scleral remodeling, and delayed myopia progression. These findings suggest that CAMKMT is required for myopia-associated scleral remodeling and ER stress, supporting its involvement in myopia pathogenesis via Ca2+-mediated signaling.