Abstract
Purpose :
Two common age-related lens pathologies, cataracts, and presbyopia are linked to age-dependent increases in lens stiffness. The mouse lens has dramatic alterations in fiber cell shapes and organization with lens age, along with increased lens stiffness. However, little is known about the relationship between observed depth-dependent cellular structures, and lens biomechanical properties. We aimed to determine lens fiber cell macro-to-nanoscale structural deformation during and after lens compression as a function of radial depth.
Methods :
Freshly dissected 8-week-old mouse lenses were compressed by application of 10 glass coverslips (CS). Images of lenses were taken with an Olympus SZ11 dissecting microscope with a digital camera, followed by fixation for scanning electron microscopy (SEM). Images of mouse fiber cells under compression and after recovery were captured by a JEOL 820 scanning electron microscope. Image analysis was performed using ImageJ.
Results :
Morphometrics analysis revealed that at 10 CS load (29% axial strain), lens axial diameter, aspect ratio, and volume decreased compared to controls while equatorial diameter increased, as expected. Upon release of load, equatorial diameter and aspect ratio recovered completely, while axial diameter and volume recovered partially. SEM revealed that cortical fiber bundle curvature increased under compression (10CS), compared to controls and recovered lenses, while nuclear fiber bundle curvature was unaffected. The paddles and protrusions of outer cortical fibers were severely distorted by compression, with a near absence of paddle-associated protrusions in the compressed lens compared to controls, while this phenomenon was rescued in the recovered lens. Notably, in SEM images of the inner cortex, the nanostructures of fiber cells were unaffected by compression, resembling the morphology of controls and recovered lenses.
Conclusions :
Our study reveals that gross lens shape change caused by mechanical strain results in ultrastructural-level changes of the lens fiber cells in a depth-dependent fashion such that the nanostructures of fiber cells are deformed in the outer cortex, but little to no deformation in the inner cortex and nucleus of the lens. This provides critical information to expand current biomechanical models of lens shape changes in terms of presbyopia and cataracts.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.