Abstract
Life-long eye lens function requires an appropriate gradient refractive index, biomechanical integrity and transparency. We conducted an extensive study of wild-type mouse lenses 1-30 months of age to define common age-related changes. Biomechanical testing and morphometrics revealed an increase in lens volume and stiffness with age. Lens capsule thickness and peripheral fiber cell widths increased between 2 to 4 months of age but not further, and thus, cannot account for significant age-dependent increases in lens stiffness after 4 months. In lenses from mice older than 12 months, we routinely observed cataracts due to changes in cell structure, with anterior cataracts due to incomplete suture closure and a cortical ring cataract corresponding to a zone of compaction in cortical lens fiber cells. Refractive index measurements showed a rapid growth in peak refractive index between 1 to 6 months of age, and the area of highest refractive index is correlated with increases in lens nucleus size with age. These data provide a comprehensive overview of age-related changes in murine lenses, including lens size, stiffness, nuclear fraction, refractive index, transparency, capsule thickness and cell structure. Our results suggest similarities between murine and primate lenses and provide a baseline for future lens aging studies.
Highlights
The eye lens is required for fine focusing of light onto the retina to form a clear image, and the function of the lens is intimately tied to its shape, biomechanical properties, transparency and refractive index
Though theoretically the lens continues to add more layers of fiber cells, there is no significant change in the lens size and shape after 18 months of age, suggesting there is a maximum size for the mouse lens
Lens stiffness continues to increase up to 30 months, indicating that increased lens size cannot explain the increase in lens stiffness
Summary
The eye lens is required for fine focusing of light onto the retina to form a clear image, and the function of the lens is intimately tied to its shape, biomechanical properties, transparency and refractive index. It has long been known that age-related changes in these lens properties lead to two major lens pathologies, cataracts and presbyopia [1]. Cataracts, defined as any lens opacity, are the leading cause of blindness in the world [2], and almost all mammalian and avian species develop age-related cataracts [3,4,5,6,7,8,9,10,11,12,13,14,15]. Changes in lens transparency occur in several locations, cortical, subcapsular and nuclear, and there are many hypothesized causes for opacities, including UV light exposure, reactive oxygen species, nutrition and genetic variations [16,17,18]. Studies have linked age-related increases in lens stiffness to presbyopia [21,22,23,24,25,26], and increased lens stiffness with age has been reported in humans [21, 26,27,28,29,30,31,32,33,34] and animal models [34,35,36], including mice [37,38,39,40,41]
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