Journal Club: Differential diagnostic of inner ear pathology by current options is challenging: mouse mutants comparison study

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Today's journal article

Ingham NJ, Steel KP. Non-invasive testing to diagnose the underlying auditory pathology of hearing impairment. 

Why I picked this article

The large majority of hearing loss is sensorineural hearing loss, where the damage occurs in the cochlea or the auditory nerve. The current clinical gap is that we cannot understand which part of the cochlea, or which cells in the cochlea, are primarily affected in a sensorineural hearing loss case. For example, whether the first damage lies in hair cells, neurons or the fluid environment in the cochlea can significantly impact the therapeutic strategy. Currently, our ability to make such a distinction in pathology types in the cochlea is very limited. 

Two of the functional assessment tools currently available that this research focuses on are auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). ABR is like an electrocardiogram, where you use electrodes to record the electrical response. Instead of recording from the heart in an electrocardiogram, with ABR, we record the electrical response from the skin behind the ear, after introducing sounds as stimuli. DPOAE is a technique to measure the function of outer hair cells, a type of auditory sensory cell in the ear, based on how the cochlear nerve amplifies the sounds coming into the ear. 

This research focused on comparing ABR and DPOAE between different mouse models of sensorineural hearing loss, to see if ABR and DPOAE can provide a distinction between different pathologies. 

Some of the research findings

Animal models:

  • The base mouse strain was C57BL/6N
  • 10 different mutant mice lines were used; they had known but different pathologies. Some had pathologies in sensory cells, others non-sensory cells, some had neural/sensory pathology while others had metabolic problems. 
  • Ages examined depended on the timing of when pathology develops, but ranged between 3-14 week-old. 
  • ABR and DPOAE parameters were normalised for each mouse mutant line, and analysed using cluster analysis. 

Findings:
  • While some trend was observed (e.g. clustering of some pathologies of sensory cells), it was not as clearly distinct as expected from previous studies in gerbils. 
  • Between different pathologies, the ABR and DPOAE profiles showed significant overlap. 
  • Authors also report that " Examination of extended parameters, such as response amplitude, did not provide any further differentiation between mice carrying different pathologies.". 

Haruna's takeaway

This is a very concise article, but massive amount of work systematically comparing 10 different mutants & control mice. To achieve the goal of this study, to evaluate differential diagnosis by ABR & DPOAE between animal models of known pathology, the approach was very comprehensive and great. The table of 10 different mouse lines used and pathologies are nicely summarised in the table within the article, and so are the cluster analyses. I thought it was a very educational publication. 

The outcome confirmed and strengthened what we already knew, that current diagnostic techniques like ABR and DPOAE alone are not sufficient. This is definitely a paper worth referencing in that grant application pitching needs a better diagnostic for inner ear pathologies. 

What a challenge we have for the inner ear.... more challenging, more exciting! 

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This is Haruna's 25/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.