Characterization of the Sheep Round Window Membrane

Abstract

Intratympanic injection is a clinically used approach to locally deliver therapeutic molecules to the inner ear. Drug diffusion, at least in part, is presumed to occur through the round window membrane (RWM), one of the two openings to the inner ear. Previous studies in human temporal bones have identified a three-layered structure of the RWM with a thickness of 70-100 μm. This is considerably thicker than the RWM in rodents, which are mostly used to model RWM permeability and assess drug uptake. The sheep has been suggested as a large animal model for inner ear research given the similarities in structure and frequency range for hearing. Here, we report the structure of the sheep RWM. The RWM is anchored within the round window niche (average vertical diameter of 2.1 ± 0.3 mm and horizontal diameter of 2.3 ± 0.4 mm) and has a curvature that leans towards the scala tympani. The centre of the RWM is the thinnest (55-71 μm), with increasing thickness towards the edges (G 171 μm), where the RWM forms tight attachments to the surrounding bony niche. The layered RWM structure, including an outer epithelial layer, middle connective tissue and inner epithelial layer, was identified with cellular features such as wavy fibre bundles, melanocytes and blood vessels. An attached "meshwork structure" which extends over the cochlear aqueduct was seen, as in humans. The striking anatomical similarities between sheep and human RWM suggest that sheep may be evaluated as a more appropriate system to predict RWM permeability and drug delivery in humans than rodent models.

Immediate-Early Modifications to the Metabolomic Profile of the Perilymph Following an Acoustic Trauma in a Sheep Model

“…Anatomically, the sheep cochlea has two and a half turns, similar to humans, and has been investigated in a computed tomography study [ 13 ]. Unlike the guinea pig, the anatomy of the round window membrane of the sheep shows multiple similarities with humans [ 14 , 15 ]. The auditory spectrum of sheep is comparable to that of humans [ 16 ], with humans having an auditory spectrum from 20 to 20,000 Hz and sheep from 100 to 30,000 Hz [ 16 , 17 ].…”

Sonoporation of the Round Window Membrane on a Sheep Model: A Safety Study

“…The anatomical structures of the sheep’s inner, middle, and outer ears are comparable with those of humans [ 36 , 37 , 38 , 39 ]. Similarities between the sheep ear and the human ear have also been found in terms of the histological composition of temporal bone structures [ 40 ], the anatomy and histology of the RWM [ 41 ], the auditory spectrum [ 41 ], and the recording of auditory brainstem responses (ABRs) [ 42 ].…”