Abstract
Purpose :
Life-long lens function requires high refractive index, biomechanical integrity and transparency. We conducted a study of wild-type murine lens properties to define the common changes that occur during aging.
Methods :
We used tissue mechanical testing, interferometric measurements of refractive index, scanning and transmission electron microscopy and live lens confocal imaging to evaluate lenses from wild-type mice between 1-30 months of age.
Results :
Biomechanical testing and morphometrics revealed a steady increase in lens stiffness with age along with an increase in lens and nuclear volume. Refractive index measurements showed a rapid growth in peak refractive index between 1 to 8 months of age, and the max refractive index of 1.55 occurred at the center of lenses from mice older than 12 months. We routinely observed anterior cataracts and distinct cortical rings in lenses from mice older than 12 months. SEM studies revealed a zone of compaction in cortical lens fiber cells near the location of the ring cataract in older lenses. TEM images showed that while young lenses had fiber cells that were hexagonal in cross section and well organized, fiber cells in old lenses were no longer hexagon and varied in size and shape. Using live confocal imaging of transgenic lenses with fluorescently-labeled cell membranes, ranging from 2 to 12 months of age, we found that capsule thickness and fiber cell widths increase in mouse lenses from 2 to 4 months of age with no additional changes in capsule thickness or fiber widths in older lenses. In contrast, while epithelial cell areas are similar in lenses from mice between the ages of 2 to 8 months, epithelial cell areas are increased in lenses from 12-month-old mice.
Conclusions :
In summary, these data provide a comprehensive overview of the changes in murine lenses with age, including alterations in lens size, stiffness, nuclear fraction, refractive index, transparency, capsule thickness and cell size. The methods we used can be adapted for study of lenses from other species. Our results suggest similarities between murine and primate lenses, including increased lens stiffness, nuclear volume and refractive index with age. Murine lenses may be a useful tool to study age-related changes in a relatively shortened period of time.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.