ROLE FOR CASPASES IN LENS FIBER DIFFERENTIATION

There is increasing evidence that programmed cell death (PCD) depends on a novel family of intracellular cysteine proteases, called caspases , that includes the Ced-3 protease in the nematode Caenorhabditis eleg ans and the interleukin-1 beta-converting enzyme (ICE)-like proteases in mammals, Some developing cells, including lens epithelial cells, er ythroblasts, and keratinocytes, lose their nucleus and other organelle s when they terminally differentiate, but it is not known whether the enzymatic machinery of PCD is involved in any of these normal differen tiation events. We show here that at least one CPP32 (caspase-3)-like member of the caspase family becomes activated when rodent lens epithe lial cells terminally differentiate into anucleate lens fibers in vivo , and that a peptide inhibitor of these proteases blocks the denucleat ion process in an in vitro model of lens fiber differentiation. These findings suggest that at least part of the machinery of PCD is involve d in lens fiber differentiation.