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

The purpose of our study was to elucidate pathways of genetically programmed cell death (apoptosis) in corneas with macular dystrophy. 10 corneal buttons (10 patients) with macular dystrophy and 8 buttons (8 patients) from enucleated eyes with chorioideal melanoma (controls) were analysed histologically. Immunohistochemical analysis was performed to investigate the presence of p21, p27, bax, cathepsin and survivin proteins. The number of positive cells was determined by analysis of 100 cells and given in percentages. The bax protein was present in 25.6% of epithelial cells in macular dystrophy corneas but was absent in controls. P21 and p27 were found in 35.7 and 87.5% of epithelial cells of macular dystrophy corneas, respectively, but again not in control tissue. In contrast, a lower percentage of cathepsin-positive (30.7% vs 58.8%) and survivin-positive cells (37.6% vs 52.1%) were present in epithelial cells of macular dystrophy corneas than in control epithelial cells. The difference reached statistical significance in the expression of p21 and p27 genes (p<0.05 in both). P21 was positive in 3% of keratocytes, p27 in 1% of endothelial cells of macular dystrophy corneas but negative in controls (0%). Bax, cathepsin and survivin immunopositivity was not detected in keratocytes or endothelial cells of either group. We conclude that the down-regulation of p21, p27 and cathepsin in epithelial cells of macular dystrophy corneas may be related to defense mechanisms against apoptotic cell death.