Mechanical and cellular response of lenses to acute ocular hypertension: Implications of AQP1 regulating water transport and lenses opacification

The morphological, mechanical, and cellular response of lenses to acute elevation of intraocular pressure (IOP) remained largely unknown. Therefore, we carried out a comprehensive study on the changes of mouse lenses after acute elevation of IOP, and explored the underlying molecular biological mechanism. Acute ocular hypertension was induced in the eye of adult C57BL/6J mice by cannulation of the anterior chamber. Gross morphology and ultrastructure of the lenses were evaluated by the slit lamp, OCT examinations, immunofluorescence staining, immunohistochemistry, and electron microscope, and physical properties were also measured. RNA sequencing analysis was applied to detect relevant transcriptional alterations. We found that subcapsular lens opacities appeared after the IOP spike. The volume, weight, and water content were subsequently decreased. While the lens capsules and LECs attached displayed no significant structural changes after IOP elevation compared with control lenses, the subcapsular cortex was compressed and disorganized. RNA sequencing analysis showed the biological changes of lenses involve various aspects such as cell adhesion and lens fiber remodeling. Lastly, we confirmed that brinzolamide eye drop was able to reduce the AQP1 level, and improve both the transparency and the water content of the lenses after IOP elevation. In conclusion, our study updates the fundamental insight towards the biomechanical response of lenses and their correlation with cataract development, paving the way for further exploration of protection towards lenses after the IOP spike. • First comprehensive analysis exploring the biochemical responses of murine lens to acute IOP elevation. • Acute elevated IOP compresses lens cortex and reduces lens volume/weight/water content, inducing subcapsular opacity. • RNA-sequencing implies altered signaling pathways of the lens in response to biomechanical stress. • Brinzolamide downregulates AQP1, restoring the lens transparency and water content post-IOP elevation.