Introduction: Previous studies by our lab indicate that neutrophils are involved with capillary degeneration in diabetic retinopathy (DR). The elastase is a serine protease in neutrophils that plays an important role in a variety of inflammatory diseases, such as chronic obstructive pulmonary disease. We are investigating the potential role of NE in the development of DR.

Method: The activity of neutrophil elastase (NE) was selectively inhibited (by daily sivelestat) or deleted (Elane-/-) from diabetic mice, and the effects of NE loss were compared to the effects of inhibition of general protease activity (over-expression of protease inhibitor, alpha-1 antitrypsin). Molecular abnormalities associated with the development of DR, including retinal superoxide production, expression of proteins associated with inflammation, and leukocyte-mediated cytotoxicity of retinal endothelial cells were used to determine the effects of NE in diabetic mice.

Result: At two months of diabetes, selective inhibition of NE or deletion of the elastase both inhibited diabetes-induced superoxide production and inflammation in the retina. Both also inhibited leukostasis and/or leukocyte mediated damage to endothelial cells in cell cytotoxicity assays. In contrast, over-expression of alpha-1 antitrypsin resulted in increased retinal superoxide production and leukocyte activity in cytotoxicity assays in both diabetic and nondiabetic animals.

Conclusion: NE may play an important role in the development of DR.


H. Liu: None. T. Kern: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at