Diabetes mellitus-induced hyperglycemia is responsible for multiple pathological ocular alternations from vasculopathy to biomechanical dyshomeostasis. Biomechanical homeostasis is crucial to maintain the normal physiological condition of the eyes. Biomechanical features vary in eye tissues regarding different anatomical positions, tissue components, and cellular functions. The disturbance in biomechanical homeostasis may result in different ocular diseases. In this review, we provide a preliminary sketch of the latest evidence on the mechano-environment of the eyeball and its possible influencing factors, thereby underscoring the relationship between the dyshomeostasis of ocular biomechanics and common eye diseases (e.g., diabetic retinopathy, keratoconus, glaucoma, spaceflight-associated neuro-ocular syndrome, retinal vein occlusion and myopia, etc.). Together with the reported evidence, we further discuss and postulate the potential role of biomechanical homeostasis in ophthalmic pathology. Some latest strategies to investigate the biomechanical properties in ocular diseases help unveil the pathological changes at multiple scales, offering references for making new diagnostic and treatment strategies targeting mechanobiology.

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Glaucoma is a highly heritable disease and myocilin was the first identified causal gene and most common pathogenic gene in glaucoma. Serine to proline mutation at position 341 of myocilin (MYOCS341P) is associated with severe glaucoma phenotypes in a five generation of primary open angle glaucoma family. But the underlying mechanisms is under explored. Here, we established MYOCS341P transgenic mouse model and characterized the glaucoma phenotypes. Further, we systematically explored the differences in function between wild-type and MYOCS341P by immunoprecipitation followed by mass spectrometry and RNA-seq analyses. We found that MYOCS341P transgenic mouse exhibit glaucoma phenotypes, characterized by reduced aqueous humor outflow, elevated intraocular pressure, decreased trabecular meshwork (TM) cells number, narrowed Schlemm’s canal, retinal ganglion cell loss, and visual impairment. Mechanistically, secretion incompetent MYOCS341P accumulated in the endoplasmic reticulum (ER), induced ER stress, and causes deregulation of autophagy, thereby promoting TM cell death. We describe an effective transgenic model for mechanistic studies and screening of therapeutic targets. And our data generated from high-throughput analyses help to elucidate the mechanism underlying mutant MYOC-related glaucoma.