Keratocyte apoptosis associated with keratoconus

Keratoconus is an ectatic corneal dystrophy associated with stromal thinnin g and disruption of Bowman's layer. The purpose of this study was to explor e a possible association between keratocyte apoptosis and keratoconus. Kera tocyte apoptosis was evaluated in corneas of patients with keratoconus, cor neas of patients with stromal dystrophies, and normal donor corneas using t he transferase-mediated dUTP-digoxigenin nick and labeling (TUNEL) assay. K eratocyte apoptosis was also studied in keratoconus and normal corneas usin g: transmission electron microscopy. TUNEL-stained keratocytes were detecte d in 60% of corneas with keratoconus, but only 35% of corneas with stromal dystrophies (P = 0.03). The number of TUNEL-positive keratocytes detected i n the keratoconus, stromal dystrophy, and normal corneas was 7+/-1 (mean+/- standard error, range 0-20), 2+/-0.8 (range 0-9), and 0+/-0 (range 0-0) TUN EL-positive cells per section, respectively. The differences between the ke ratoconus and the stromal dystrophy (P = 0.0097) or the normal cornea (P = 0.01) groups were statistically significant. The difference between the str omal dystrophy and normal cornea groups was not statistically significant ( P = 0.45). The stromal dystrophy group was included to account for surgery- associated keratocyte apoptosis. No TUNEL-stained keratocytes were detected in normal corneas. Cell morphologic changes consistent with apoptosis were detected by transmission electron microscopy (TEM) in keratocytes of kerat oconus corneas, but not in keratocytes in normal corneas. Chronic keratocyt e apoptosis associated with ongoing epithelial. injury may link risk factor s associated with keratoconus such as chronic eye rubbing, contact lens wea r, or atopic eye disease. Similarly, increases that have been detected in s everal different degradative enzymes in keratoconus corneas could be associ ated with chronic keratocyte apoptosis and less than perfect control of rel ease of intracellular contents. (C) 1999 Academic Press.