TAT-mediated PRDX6 protein transduction protects against eye lens epithelial cell death and delays lens opacity

1 Department of Ophthalmology, University of Fukui, Fukui, Japan; 2 Department of Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska; 3 Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and 4 Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska Submitted 14 November 2007 ; accepted in final form 7 January 2008 A diminished level of endogenous antioxidant in cells/tissues is associated with reduced resistance to oxidative stress. Peroxiredoxin 6 (PRDX6), a protective molecule, regulates gene expression/function by controlling reactive oxygen species (ROS) levels. Using PRDX6 protein linked to TAT, the transduction domain from human immunodeficiency virus type 1 TAT protein, we demonstrated that PRDX6 was transduced into lens epithelial cells derived from rat or mouse lenses. The protein was biologically active, negatively regulating apoptosis and delaying progression of cataractogenesis by attenuating deleterious signaling. Lens epithelial cells from cataractous lenses bore elevated levels of ROS and were susceptible to oxidative stress. These cells harbored increased levels of active transforming growth factor (TGF)-β1 and of -smooth muscle actin and βig-h3, markers for cataractogenesis. Importantly, cataractous lenses showed a 10-fold reduction in PRDX6 expression, whereas TGF-β1 mRNA and protein levels were elevated. The changes were reversed, and cataractogenesis was delayed when PRDX6 was supplied. Results suggest that delivery of PRDX6 can postpone cataractogenesis, and this should be an effective approach to delaying cataracts and other degenerative diseases that are associated with increased ROS. reactive oxygen species; transforming growth factor-β; βig-h3; -smooth muscle actin; oxidative stress Address for reprint requests and other correspondence: D. P. Singh, Dept. of Ophthalmology and Visual Sciences, 895540 Nebraska Medical Center, Omaha, NE 68198-6395 (e-mail: dpsingh{at}unmc.edu )