3D visualization of cellular and molecular distributions in human crystalline lenses at different ages.

Background: The human lens is a highly organized tissue, and it is constructed of delicate inner architectures that ensure its transparency. However, the pattern of cell distribution in the intact lens has rarely been observed or traced in a three-dimensional (3D) perspective.

Methods: Here, we modified and compared three different kinds of tissue transparency methods to investigate the cellular and molecular changes in the human lens at different ages from a 3D perspective.

Results: First, we analyzed the general 3D parameters of cleared human lenses from 6 months to 72 years of age and found that the equator proportion remained constant with age (23.05% ± 0.36). Next, we visualized the cellular distribution patterns in the anterior capsule and equator, as well as the distribution of cortical fiber cells. Interestingly, we observed the accumulation of equatorial epithelium in adolescents and the asymmetrical denucleation of cortical fiber cells in the elderly. Zonula occludens-1 and tropomyosin receptor kinase A were also identified in the pre-equatorial germinative zone, and its presence decreased when comparing lenses of a 17-year-old to those of a 49-year-old.

Conclusion: We present a 3D cellular and molecular reconstruction of the human lens, illustrating the observed alterations in human lens epithelial cells across different ages.