Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms

Abstract

Based on the histological results of this study, the progressive development of chronic TMPs appeared to be associated with increased epidermal thickening, collagen and keratin deposition, macrophage infiltration and reduced cellular proliferation. After the 3-4 weeks of transition phase, the TMPs seemed to have transformed into a non-healing chronic TMP between 6 and 10 weeks.

Animal Model of Chronic Tympanic Membrane Perforation

“…Despite attempts to develop an animal model for chronic TMP as far back as 1992, recent reviews of the literature still call for a reliable, clinically relevant model (Amoils et al, ; Santa Maria et al, ; Wang et al, ). The animal models that have gained the most acceptance are the “infolding technique” (Amoils et al, ), and a newer model developed by Wang et al which uses topical dexamethasone and mitomycin along with ventilation tube insertion to generate chronic TMP in mice, this latter with a success rate of approximately 80% of non‐closure between 8 and 10 weeks (Wang et al, ). Additionally, Santa Maria et al () published three different mouse models of TMP using OSU8‐1 (a hydroxamate‐based metalloproteinase inhibitor that inhibits ligands that interact with epidermal grow factor receptors) (Umeda et al, ), obstructing the Eustachian tube and a model of chronic suppurative otitis media, reporting at least a 87.9% of patency of TMP after 3 months.…”

“…The animal models that have gained the most acceptance are the "infolding technique" (Amoils et al, 1992), and a newer model developed by Wang et al which uses topical dexamethasone and mitomycin along with ventilation tube insertion to generate chronic TMP in mice, this latter with a success rate of approximately 80% of non-closure between 8 and 10 weeks (Wang et al, 2017). Additionally, Santa Maria et al (2015) published three different mouse models of TMP using OSU8-1 (a hydroxamate-based metalloproteinase…”

“…Animal models of delayed TMP have been recently described (Santa Maria et al, ; Santa Maria et al, ; Wang et al, ) showing varying results with controversy still existing on the minimal time of perforation patency to be considered clinically relevant. Authors have suggested that a patency period ranging from 8 to12 weeks is the minimum time for a perforation to be considered chronic (Truy et al, ; Deng et al, ; Santa Maria et al, ; Wang et al, ; Kuo et al, ). Techniques used for delaying spontaneous closure of TMP included infolding the edges of the perforation (Emami et al, ), thermal injury (Amoils et al, ), re‐myringotomy (Wang et al, ), topical application of agents that delay epithelization such as dexamethasone (Wang et al, ), mitomycin C (Wang et al, ), hydrocortisone (Spandow and Hellstrom, ), and glutaraldehyde (Truy et al, ).…”

“…Authors have suggested that a patency period ranging from 8 to12 weeks is the minimum time for a perforation to be considered chronic (Truy et al, 1995;Deng et al, 2009;Santa Maria et al, 2017;Wang et al, 2017;Kuo et al, 2018). Techniques used for delaying spontaneous closure of TMP included infolding the edges of the perforation (Emami et al, 2014), thermal injury (Amoils et al, 1992), re-myringotomy (Wang et al, 2014), topical application of agents that delay epithelization such as dexamethasone (Wang et al, 2017), mitomycin C (Wang et al, 2017), hydrocortisone (Spandow and Hellstrom, 1993), and glutaraldehyde (Truy et al, 1995). Moreover, models using transgenic mice have also been shown useful for creating long-lasting perforations (Li et al, 2006;Shen et al, 2012;Shen et al, 2014).…”

Chronification of Tympanic Perforation with Mitomycin C in a Rat Model

“…Recent studies by Wang et al (22) have used a similar method although they obtained perforations of insufficient duration to establish and constitute a chronicity model. The difference is probably related to the method used since these authors employed a higher dose of mitomycin, different from the one recommended in the Jassir et al (4) work.…”