CD24 is required for sustained transparency of the adult lens.

Genes regulate, maintain, and fine-tune the structural organization and physiological homeostasis of the lens and therefore influence lens transparency. RNAseq profiling of the mouse lens revealed that the Cd24a gene, which encodes the mucin-like GPI-linked membrane protein CD24, is abundantly expressed in the lens. Immunolocalization revealed that CD24 protein is abundant at mouse lens fiber cell membranes from early lens development into adulthood, while in adult human lenses, CD24 protein was detected in both the lens epithelium and fibers. Analysis of mice lacking the Cd24a gene revealed that the lens develops normally and is transparent with normal morphology until 2 months of age. However, older Cd24a null mice have smaller than normal lenses which exhibit abnormal fiber cell structure, actin filament disorganization, and refractive defects that lead to premature cataract development by 1 year of age. By integrating RNA sequencing, immunofluorescence, and magnetic resonance imaging, we found that the aquaporin 1 gene that regulates lens epithelial water transport is downregulated and the protein gradient that mediates the lenses refractive properties is altered in aged Cd24a null lenses that exhibit cataract. However, experiments on intracellular gap junction coupling and hydrostatic pressure in 2 month old lenses found no differences between control and Cd24a null lenses, suggesting that the later lens defects do not arise from primary issues with the lens circulation. Overall, our study found that CD24 plays a key role in maintaining the structural organization and refractive properties of the adult lens.