P21, p27, bax, cathepsin and survivin pathways in macular dystrophy corneas

Abstract

The purpose of our study was to elucidatepathways of genetically programmed cell death(apoptosis) in corneas with macular dystrophy.10 corneal buttons (10 patients) with maculardystrophy and 8 buttons (8 patients) from enucleatedeyes with chorioideal melanoma (controls) wereanalysed histologically. Immunohistochemical analysiswas performed to investigate the presence of p21, p27,bax, cathepsin and survivin proteins. The number ofpositive cells was determined by analysis of 100 cellsand given in percentages.The bax protein was present in 25.6% of epithelialcells in macular dystrophy corneas but was absent incontrols. P21 and p27 were found in 35.7 and 87.5% ofepithelial cells of macular dystrophy corneas,respectively, but again not in control tissue. In contrast, alower percentage of cathepsin-positive (30.7% vs58.8%) and survivin-positive cells (37.6% vs 52.1%)were present in epithelial cells of macular dystrophycorneas than in control epithelial cells. The differencereached statistical significance in the expression of p21and p27 genes (p<0.05 in both).P21 was positive in 3% of keratocytes, p27 in 1% ofendothelial cells of macular dystrophy corneas butnegative in controls (0%). Bax, cathepsin and survivinimmunopositivity was not detected in keratocytes orendothelial cells of either group. We conclude that the down-regulation of p21, p27and cathepsin in epithelial cells of macular dystrophycorneas may be related to defense mechanisms againstapoptotic cell death.