Cochlear histopathology in human genetic hearing loss: State of the science and future prospects

• Published in: Hearing research 2019-10, Vol.382, p.107785-107785, Article 107785
• Main Authors: Bommakanti, Krishna, Iyer, Janani S., Stankovic, Konstantina M.
• Format: Article
• Language: English
• Subjects: Animals; Cochlea - pathology; Cochlea - physiopathology; Disease Models, Animal; Genetic Predisposition to Disease; Genetic Therapy; Hearing - genetics; Hearing loss; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - pathology; Hearing Loss, Sensorineural - physiopathology; Hearing Loss, Sensorineural - therapy; Histopathology; Humans; Mice, Mutant Strains; Mutation; Phenotype; Species Specificity; Temporal bone
• ISSN: 0378-5955; 1878-5891; 1878-5891
• DOI: 10.1016/j.heares.2019.107785

Sensorineural hearing loss (SNHL) is an extraordinarily common disability, affecting 466 million people across the globe. Half of these incidents are attributed to genetic mutations that disrupt the structure and function of the cochlea. The human cochlea's interior cannot be imaged or biopsied without damaging hearing; thus, everything known about the morphologic correlates of hereditary human deafness comes from histopathologic studies conducted in either cadaveric human temporal bone specimens or animal models of genetic deafness. The purpose of the present review is to a) summarize the findings from all published histopathologic studies conducted in human temporal bones with known SNHL-causing genetic mutations, and b) compare the reported phenotypes of human vs. mouse SNHL caused by the same genetic mutation. The fact that human temporal bone histopathologic analysis has been reported for only 22 of the nearly 200 identified deafness-causing genes suggests a great need for alternative and improved techniques for studying human hereditary deafness; in light of this, the present review concludes with a summary of promising future directions, specifically in the fields of high resolution cochlear imaging, intracochlear fluid biopsy, and gene therapy. •Sensorineural hearing loss is the most common sensory deficit, disabling 466 million people.•Human cochlear histopathology has been reported for only 20 of nearly 200 deafness-causing genes.•We present human temporal bone histopathology analyzed across all causes of genetic hearing loss.•Our analysis highlights the need for cellular-level diagnostic tools in living people.