Acute eardrum perforation is caused by pressure changes, trauma and infection. In most cases, the tympanic membrane (eardrum) heals with no scarring and full function is restored. However, in 6% of cases the tympanic membrane does not fully heal and there are limited treatment options for chronic perforation, with most relying on surgery. Although similar to skin wound healing, there are distinct differences in tympanic membrane healing that need to be better understood.
In this study, Dinwoodie, Tucker and Fons used transgenic reporter mice to track wound healing in the three distinct layers of the tympanic membrane. The authors precisely perforated all three layers of the membrane: outer epithelial layer (OEL), lamina propria (LP) and inner mucosal layer (IML). They then found that at 2 days post perforation (dpp), the OEL, but not the LP or IML, retracted further from the perforation site. Between 5 and 7 dpp, the OEL thickened with cells migrating over the wound site, forming a scaffold of undifferentiated keratinocytes that later matured at 10 dpp. At 5 dpp, the IML also began to thicken at the wound margin, as did the LP at 7 dpp due to proliferation of the neural crest-derived cells. The authors then showed that the OEL scaffold allowed the LM and IML to bridge over the perforation site, alongside invading vasculature at 8 dpp, with these layers thickening by 10 dpp. Between 10 and 15 dpp, the OEL – the layer that increased in thickness the most – underwent significant remodelling to return to a functional thin layer, as an epithelial cap was removed by cornification, which is a form of programmed cell death. The authors noticed that, at 15 dpp, all layers had returned to their original thickness and vasculature had retracted from the site of injury, but that some cell morphology changes were present. By 30 dpp, no signs of injury were apparent in the tympanic membrane.
Studying the three distinct and very thin layers of the tympanic membrane can be extremely challenging. In this study, the team was able to track the role of each layer in wound healing in a precise and temporal manner. By expanding our understanding of how the tympanic membrane heals under normal conditions, this study could lead to the development of targeted therapies that enhance repair in acute and chronic cases of perforation.
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