Role of JAM-C in lens cell adhesion, calcium homeostasis, and cataract pathogenesis.

Abstract

Junctional adhesion molecule C (JAMC) mutations are associated with autosomal recessive forms of cataracts. Our previous studies characterized the features of nuclear cataracts and revealed abnormal lens development and differentiation in Jamc knockout (Jamc-KO) mice. However, the pathogenic mechanisms underlying cataract formation following JAMC deletion remain largely unclear. In this study, we further investigated lens impairments in Jamc-KO mice. We found that JAM-C plays a critical role in maintaining lens cell adhesion and preserving the integrity of ball-and-socket junctions. Moreover, JAM-C deficiency led to elevated intracellular Calevels in lens cells, accompanied by degradation of IIα spectrin and F-actin cytoskeletal protein, suggesting calpain activation. In addition, JAM-C was found to regulate FGF/ERK signaling in lens epithelial cells (LEC). Collectively, these findings indicate that JAM-C is essential for lens cell-cell adhesion and junctional function, and that disruption of calcium homeostasis may ultimately contribute to lens structural damage and cataract formation. Our study highlights the role of JAM-C in maintaining lens structure and homeostasis and provides new insights into the pathogenic mechanisms of JAM-C-related cataracts.