dissection-adult-mouse-stria-vascularis-for-single-nucleus-sequencing

Dissection of Adult Mouse Stria Vascularis for Single-Nucleus Sequencing or Immunostaining

Endocochlear potential, which is generated by the stria vascularis, is essential to maintain an environment conducive to appropriate hair cell ...

National Institutes of Health

To identify genes implicated in sudden sensorineural hearing loss (SSNHL) and localize their expression in the cochlea to further explore potential pathogenic mechanisms and therapeutic targets.

Utilizing Single Cell RNA-Sequencing to Implicate Cell Types and Therapeutic Targets for SSNHL in the Adult Cochlea.

Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation or sudden changes in hearing, including sudden sensorineural hearing loss (SSNHL), Meniere's disease (MD), and autoimmune inner ear disease (AIED). Despite their use across these diseases, the rate of complete recovery remains low, and results across the literature demonstrates significant heterogeneity with respect to the effect of corticosteroids, suggesting a need to identify more efficacious treatment options. Previously, our group has cross-referenced steroid-responsive genes in the cochlea with published single-cell and single-nucleus transcriptome datasets to demonstrate that steroid-responsive differentially regulated genes are expressed in spiral ganglion neurons (SGN) and stria vascularis (SV) cell types. These differentially regulated genes represent potential druggable gene targets. We utilized multiple gene target databases (DrugBank, Pharos, and LINCS) to identify orally administered, FDA approved medications that potentially target these genes. We identified 42 candidate drugs that have been shown to interact with these genes, with an emphasis on safety profile, and tolerability. This study utilizes multiple databases to identify drugs that can target a number of druggable genes in otologic disorders that are commonly treated with steroids, providing a basis for establishing novel repurposing treatment trials.

Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease.

The stria vascularis (SV) has been shown to play a critical role in the pathogenesis of many diseases associated with sensorineural hearing loss (SNHL), including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL), hereditary hearing loss (HHL), and drug-induced hearing loss (DIHL), among others. There are a number of other disorders of hearing loss that may be relatively neglected due to being underrecognized, poorly understood, lacking robust diagnostic criteria or effective treatments. A few examples of these diseases include autoimmune inner ear disease (AIED) and/or autoinflammatory inner ear disease (AID), Meniere's disease (MD), sudden sensorineural hearing loss (SSNHL), and cytomegalovirus (CMV)-related hearing loss (CRHL). Although these diseases may often differ in etiology, there have been recent studies that support the involvement of the SV in the pathogenesis of many of these disorders. We strive to highlight a few prominent examples of these frequently neglected otologic diseases and illustrate the relevance of understanding SV composition, structure and function with regards to these disease processes. In this study, we review the physiology of the SV, lay out the importance of these neglected otologic diseases, highlight the current literature regarding the role of the SV in these disorders, and discuss the current strategies, both approved and investigational, for management of these disorders.

Article	Year
Utilizing Single Cell RNA-Sequencing to Implicate Cell Types and Therapeutic Targets for SSNHL in the Adult Cochlea. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology\| PubMed ID: 34510123	2021
Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease. Biomolecules\| PubMed ID: 36358991	2022
The role of the stria vascularis in neglected otologic disease. Hearing research\| PubMed ID: 36584545	2023

J. Dixon Johns

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