Transferrin in after-cataract and as a survival factor for lens epithelium

The Fe-transport protein, transferrin (Tf), is synthesized and secreted by whole lenses and cultured lens epithelial cells. Because of Tf's central role in cell growth and proliferation, its participation in lens cell proliferation following cataract extraction was explored using a rabbit model of after-cataract. Varying amounts of the central anterior lens capsule were removed (0, 35, or 80%) following extraction of the lens. The Tf content of and secretion by after-cataract lens capsular sacs containing regenerated lens tissue was determined ex vivo at 0, 3, 5, 7 and 9 weeks post-surgery. In all cases Tf content of and secretion by the lens sacs was higher than that of their contralateral controls (whole lenses). Tf secretion was up to 5-fold higher and metabolic labeling studies indicated secretion of newly synthesized Tf. The sacs contained up to 10 times the concentration of Tf as the control lenses. Human lens after-cataract capsular bags also secreted Tf. The function of Tf as a survival factor was tested on cultured lens epithelial cells. Cells cultured in serum-free medium had a survival rate of only 20-34% if the medium was changed each day. If the medium was never changed during this period, the survival rate was 43-52%, suggesting secretion of essential growth factors by these cells. Addition of 200 microg ml-1 Tf to the medium during each daily change increased survival to levels attained when the medium was not changed. Addition of Tf antibodies to the culture medium during each daily change decreased cell survival to 14%. Apparently Tf acts as a survival factor for lens epithelia and its synthesis is up-regulated in after-cataract lens sacs. These factors suggest that Tf may play an important role in the pathogenesis of lens epithelial cell proliferation and after-cataract formation following cataract surgery.