Fig. 10.

A diagram illustrating the potential roles of p53 and Acvr1 in the formation of PSCs. (A) In wild-type lenses, the occasional fiber cells that fail to withdraw from the cell cycle are eliminated by apoptosis in a largely p53-dependent manner. (B) In Acvr1^CKO lenses, a few fiber cells fail to exit from the cell cycle. These abnormal cells are eliminated by p53-dependent and p53-independent mechanisms. (C) In Trp53^CKO lenses, an increased percentage of fiber cells continue to proliferate. Owing to the absence of p53, some of these cells are not removed by apoptosis. If these cells divide, one of the daughter cells will remain attached to its neighbors at the anterior surface of the fiber mass and the other will adhere to the posterior capsule. Cells remaining adherent to the capsule round up and move to the posterior pole, where they form a plaque of epithelioid cells. Acvr1 signaling prevents these cells from proliferating. Cells that accumulate beneath the lens epithelium can degenerate or be phagocytosed by epithelial cells. (D) In Acvr1;Trp53^DCKO lenses, a substantial percentage of fiber cells proliferate, do not get eliminated by p53-mediated apoptosis and accumulate at the posterior pole of the lens. Because Acvr1 is absent, these cells continue to proliferate, leading to the formation of a large, subcapsular mass that might later form a vascularized tumor.