Molecular mechanisms of endolymphatic hydrops and treatments for Meniere's disease

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Steroid treatment for patients with inner ear disorders including Meniere's disease is usually performed, however the mechanism of steroid effects remains to be clarified. The aquaporins (AQPs) are a family of small transmembrane water transporters. It has been recently revealed that it makes a role in regulating homeostasis in the inner ear fluids. To elucidate action points of steroids in the inner ear, we first identified AQP1, 2, 3, 4, 5 and 6 mRNAs in the rat cochlea and AQP1, 3, 4, 5 and 6 in the rat endolymphatic sac by means of RT-PCR. Then, we found that intratympanic injections of steroids upregulated AQP1 mRNA of the rat cochlea in a dose-dependenct manner. These results suggest that steroids may be effective on the water homeostasis in the rat inner ear mainly via AQP1.The next aim of our study is to see if the endolymphatic sac is really available as a drug delivery system to make effects on the inner ear organs. We examined effects of a single insertion of dexamethasone into the rat unilateral endolymphatic sac on mRNA expression of the inner ear AQP family, transmembrane water transporters and putative endolymphatic fluid modulators, by means of real-time quantitative PCR. Only AQP-3 mRNA expression in the ipsilateral cochlea was significantly up-regulated in comparison with controls and the up-regulation was demonstrated both in dose-dependent and time-dependent manners. These findings suggest that the intra-endolymphatic sac steroids could make regulatory effects on the inner ear AQP-3 expression via vestibular aqueduct and modulate the homeostasis of endolymphatic fluids, encouraging the possibility that the endolymphatic sac could be a therapeutic window for the inner ear disease.