Developmental and Protective Mechanisms of the Ocular Lens.

The vertebrate eye lens functions to focus light onto the retina to produce vision.
The lens is composed of an anterior monolayer of cuboidal epithelial cells that overlie a
core of organelle free fiber cells. The lens develops and grows throughout life by the
successive layering of lens fiber cells via their differentiation from lens epithelial cells.
Lens developmental defect and damage to the lens are associated with cataract formation,
an opacity of the lens that is a leading cause of visual impairment worldwide. The only
treatment to date for cataract is by surgery. Elucidating those molecules and mechanisms
that regulate the development and lifelong protection of the lens is critical toward the
development of future therapies to prevent or treat cataract. To determine those
molecules and mechanisms that may be important for these lens requirements we
employed high-throughput RNA sequencing of microdissected differentiation statespecific
lens cells to identify an extensive range of transcripts encoding proteins expressed by these functionally distinct cell types. Using this data, we identified
differentiation state-specific molecules that regulate mitochondrial populations between
lens epithelial cells that require the maintenance of a functional population of
mitochondria and lens fiber cells that must eliminate their mitochondria for their
maturation. In addition, we discovered a novel mechanism for how lens epithelial cells
clear apoptotic cell debris that could arise from damage to the lens and found that UVlight
likely compromises this system. Moreover, the data herein provide a framework to
determine novel lens cell differentiation state-specific mechanisms. Future studies are
required to determine the requirements of the identified molecules and mechanisms
during lens development, lens defense against damage, and cataract formation.