Can you hear me now? A genetic model of otitis media with effusion

Abstract

Otitis media with effusion (OME) is characterized by the occurrence of fluid in the middle-ear cavity in the absence of any signs of acute ear infection and occurs most frequently in children with auditory or eustachian tube dysfunction. Its chronic form is an important clinical issue for pediatricians and otologists alike. The study by Depreux et al. in this issue of the JCI shows that absence of the transcriptional activator Eya4 in knockout mice results in abnormal structuring of the eustachian tube, thus predisposing these animals to OME (see the related article beginning on page 651). The development of this genetics-based animal model is an important advance for understanding OME and for exploring new avenues of treatment.

Figure 1. ET physiology.

(A) The normal ET. The ET, which joins the nasopharynx at the torus tubarius and joins the middle-ear cavity at the ostium, permits airflow between the middle-ear cavity and nasopharynx, balancing middle-ear pressure with ambient air pressure. Also, middle-ear secretions are swept into the nasopharynx (clearance) from the middle-ear cavity. (B) Mechanical obstruction of the ET may occur at the torus tubarius by adenoid hypertrophy or edema (B), or at the ostium in the middle-ear cavity by perhaps a polyp or a cholesteatoma (C). The pathologies shown in B or C block air flow and the clearance of middle-ear cavity secretions though the ET, increasing middle-ear negative pressure (P^–) and accumulation of middle-ear secretions. An intrinsic ET obstruction may also result from epithelium inflammation (D), secondary to nasal infection or allergy. This also results in middle-ear negative pressure and secretion accumulation. TM, tympanic membrane.

Figure 2. Dysmorphology of the ear in Eya4^–/– mice is characteristic of human OME.

(A) Schematic of normal morphology of the middle-ear cavity and ET in WT mice. (B) In this issue of the JCI, Depreux et al. (6) report a critical role for the transcriptional activator Eya4 in structuring the ET and in its positioning within the middle ear in mice. In Eya4^–/– mice, which are profoundly deaf, the ET epithelium was swollen and the medial osseous portion of the ET that opens into the middle-ear cavity was markedly narrowed and malpositioned at the anterior perimeter of the middle-ear cavity. The opening of the ET at the ostium was blocked by a polyp in 10% of Eya4^–/– animals. These structural abnormalities appeared to predispose the mutant animals to the development of OME-like symptoms, including tympanic membrane retraction, inflammation of middle-ear cavity mucosa, and accumulation of middle-ear secretions (with or without bubbles). The results increase our knowledge of the genetic determinants of middle-ear development, and this animal model will be useful for the development of new therapies for genetic and possibly acquired forms of human OME.