Inhibition of matrix metalloproteinases in gerbil cholesteatoma: Preliminary findings

Abstract

This study was conducted to examine the role of matrix metalloproteinases (MMPs) and the impact of a topical MMP inhibitor, ilomostat, on the development of tympanic membrane (TM) atelectasis in the gerbil model. Eustachian tubes were cauterized bilaterally in 19 gerbils. Thereafter, both TMs received once-daily topical treatment for 8 weeks with ilomostat or vehicle or no treatment (n = 6 or 7 per group). TM atelectasis was serially graded, and TMs were harvested at 8 weeks. Gelatin zymograms were performed to determine MMP activity. The mean activity levels of proenzyme and active MMP-9 and MMP-2 and degree of atelectasis did not differ between groups. TM atelectasis did not correlate to levels of enzymes across individual samples. Topical application of an MMP inhibitor did not significantly prevent the development of TM atelectasis. It remains to be determined whether the use of MMP inhibitors may prevent the progression of atelectasis in humans.