Interleukin-1α downregulates extracellular-superoxide dismutase in human corneal keratoconus stromal cells

PURPOSE: The purpose of this investigation was to elucidate the regulation of corneal extracellular superoxide dismutase (SOD3) synthesis in keratoconus. We compared the basal and cytokine-regulated SOD3 synthesis in cultured human stromal cells from keratoconus corneas to stromal cells from normal and bullous keratopathy corneas. METHODS: Keratocyte cultures were obtained from patients undergoing corneal transplantation for keratoconus and bullous keratopathy, and from healthy donor corneas. The cell lines obtained were cultured until near confluence and interleukin-1 alpha, interleukin-6, transforming growth factor beta, or platelet derived growth factor were added to the media. The phenotypes of the cultured cells were assessed by immunocytochemical expression of alpha-smooth muscle actin and CD34. SOD3 protein contents were determined in the culture media with ELISA after 24, 48, 72, and 96 h. RESULTS: Interleukin-1 alpha had an inhibitory effect on SOD3 synthesis exclusively in the keratoconus cultures (p < 0.01). Platelet derived growth factor induced a reduction in SOD3 synthesis in all groups (p < 0.05). CONCLUSIONS: Here, we demonstrate that cultured keratoconus stromal cells respond with a reduced SOD3 synthesis to interleukin-1 alpha, which is not the case in corresponding normal or bullous keratopathy cells. Since interleukin-1 alpha is upregulated in corneal trauma and inflammation, keratoconus corneas may muster an insufficient oxidative defense under such conditions.