Effect of Immunophilin Inhibitors on Cochlear Fibroblasts and Spiral Ganglion Cells.

Audiol Neurootol

Department of Otorhinolaryngology, Hannover Medical School, Hannover, Germany.

Published: January 2023

AI Article Synopsis

  • Loss of hair cells and spiral ganglion neurons (SGN) contributes to hearing loss, and cochlear implant success is linked to the number of surviving SGN.
  • Using immunophilin inhibitors MM284 and V20 in vitro on SGN and fibroblasts showed that these substances may reduce inflammatory effects without hindering immune function.
  • Results indicated that MM284 and V20 had no negative impact on SGN survival or metabolic activity at low concentrations, particularly suggesting MM284 as a potential candidate for cochlear applications.

Article Abstract

Introduction: Loss of hair cells and degeneration of spiral ganglion neurons (SGN) lead to severe hearing loss or deafness. The successful use of a cochlear implant (CI) depends among other factors on the number of surviving SGN. Postoperative formation of fibrous tissue around the electrode array causes an increase in electrical impedances at the stimulating contacts. The use of immunophilin inhibitors may reduce the inflammatory processes without suppressing the immune response. Here, we report on in vitro experiments with different concentrations of immunophilin inhibitors MM284 and compound V20 regarding a possible application of these substances in the inner ear.

Methods: Standard cell lines (NIH/3T3 fibroblasts), freshly isolated SGN, and fibroblasts from neonatal rat cochleae (p3-5) were incubated with different concentrations of immunophilin inhibitors for 48 h. Metabolic activity of fibroblasts was investigated by MTT assay and cell survival by counting of immunochemically stained neurons and compared to controls.

Results: MM284 did not affect SGN numbers and neurite growth at concentrations of 4 × 10-5 mol/L and below, whereas V20 had no effect at 8 × 10-6 mol/L and below. Metabolic activity of fibroblasts was unchanged at these concentrations.

Conclusion: Especially MM284 might be considered as a possible candidate for application within the cochlea.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909619PMC
http://dx.doi.org/10.1159/000526454DOI Listing

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