Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome.

Betsy Szeto, Chris Valentini, Aykut Aksit, Emily G Werth, Shahar Goeta, Lewis M Brown, Elizabeth S Olson, Jeffrey W Kysar, Anil K Lalwani

Journal of proteome research 2021 Aug 06

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Glucocorticoids are the first-line treatment for sensorineural hearing loss, but little is known about the mechanism of their protective effect or the impact of route of administration. The recent development of hollow microneedles enables safe and reliable sampling of perilymph for proteomic analysis. Using these microneedles, we investigate the effect of intratympanic (IT) versus intraperitoneal (IP) dexamethasone administration on guinea pig perilymph proteome. Guinea pigs were treated with IT dexamethasone (n = 6), IP dexamethasone (n = 8), or untreated for control (n = 8) 6 h prior to aspiration. The round window membrane (RWM) was accessed via a postauricular approach, and hollow microneedles were used to perforate the RWM and aspirate 1 μL of perilymph. Perilymph samples were analyzed by liquid chromatography-mass spectrometry-based label-free quantitative proteomics. Mass spectrometry raw data files have been deposited in an international public repository (MassIVE proteomics repository at https://massive.ucsd.edu/) under data set # MSV000086887. In the 22 samples of perilymph analyzed, 632 proteins were detected, including the inner ear protein cochlin, a perilymph marker. Of these, 14 proteins were modulated by IP, and three proteins were modulated by IT dexamethasone. In both IP and IT dexamethasone groups, VGF nerve growth factor inducible was significantly upregulated compared to control. The remaining adjusted proteins modulate neurons, inflammation, or protein synthesis. Proteome analysis facilitated by the use of hollow microneedles shows that route of dexamethasone administration impacts changes seen in perilymph proteome. Compared to IT administration, the IP route was associated with greater changes in protein expression, including proteins involved in neuroprotection, inflammatory pathway, and protein synthesis. Our findings show that microneedles can mediate safe and effective intracochlear sampling and hold promise for inner ear diagnostics.

Citation

Betsy Szeto, Chris Valentini, Aykut Aksit, Emily G Werth, Shahar Goeta, Lewis M Brown, Elizabeth S Olson, Jeffrey W Kysar, Anil K Lalwani. Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome. Journal of proteome research. 2021 Aug 06;20(8):4001-4009