Alteration in the Yap Signaling Pathway in Cataractous Human Lens Epithelium.

PURPOSE: The loss of SOX2+GJA1- lens epithelial stem cells, along with a decrease in sphere-forming ability, was observed in the central zone of cataractous lenses. Nuclear localization of Yes-associated protein (YAP) has been associated with stemness in various tissues, and its conditional knockout was reported to develop cataract in mice. This study aims to investigate the expression of YAP and SOX2, along with other YAP signaling genes, in the anterior human lens epithelium of normal and cataractous lenses.

METHODS

Whole mounts of human anterior lens epithelium from normal and cataract lenses were immunostained for SOX2, YAP, and α-SMA, followed by confocal microscopic analysis. Further, the expression of YAP signaling genes was analyzed by Western blot.

RESULTS

Nuclear expression of SOX2 and YAP was identified in the central (7.25 ± 3.63% of cells) and equatorial (9.15 ± 6.09% of cells) zones of normal lens epithelium. Such cells were absent in cataractous lenses along with a significant reduction in nuclear YAP expression. Western blot analysis confirmed the increased pYAP/YAP ratio and decreased MST2 and LATS1 in cataractous lens compared to normal lens epithelium. Furthermore, α-SMA expression was elevated in cataractous lens epithelium, indicating its association with cataract development.

CONCLUSION

The absence of SOX2+YAP+ cells in cataractous lenses indicated the possible association between stem cells and cataract development. Further studies are essential to elucidate the role of YAP signaling in the pathogenesis of cataract.