Fas-mediated apoptosis in human lens epithelial cells of cataracts associated with diabetic retinopathy.

Abstract

This study was designed to detect apoptosis in both human senile cataracts and cataracts associated with diabetic retinopathy (DR) and to elucidate the signaling pathway involved in its regulation. Samples of human cataracts were obtained from 56 patients (senile cataracts, n = 40; cataracts with DR, n = 16) and were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method, transmission electron microscopy, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) assay of apoptotic modulators. The TUNEL study demonstrated that the percentage of TUNEL-positive cells in the cataracts with proliferative DR was higher than in the senile cataracts ( P < 0.05). The immunohistochemistry and RT-PCR assay showed a higher level of Fas expression and Fas mRNA in the cataracts with DR than in the senile cataracts, although there was no difference in the expression level of the Fas ligand, Bcl-2, and their mRNAs between both groups. The number of dark cells, which were characterized by a convoluted nucleus and chromatin condensation with abundant free 3'-OH DNA ends, was higher in the cataracts with DR than in the senile cataracts ( P < 0.01). Apoptosis plays an important role in the development of cataracts with DR, but not in senile cataracts, and may be induced by Fas-mediated signaling.