gms | German Medical Science

Introduction: To study the molecular mechanism of adaptation to hypoxia in the inner ear tissues, we used organotypic cochlear cultures. The expression of apoptosis-related genes induced by normoxic and hypoxic culture conditions was determined.

Methods: mRNA expression from the organ of Corti (OC), modiolus (MOD) and stria vascularis (SV) freshly isolated from newborn rats (3-5 days old) was compared to the mRNA expression from tissues cultured 24 h under normoxic and hypoxic conditions using microarray and quantitative real time RT-PCR.

Results: In the control fresh tissues, superoxide dismutase 1 (SOD-1) and calpain-1 mRNA were most prominently expressed. Normoxic culture induced remarkable region-specific changes of SODs and caspases. In the OC, SODs remained unchanged, but the pro-apoptotic genes caspase-2, caspase-3, caspase-6 and calpain-1 decreased. In the MOD, the mitochondrial SOD-2 and the extracellular SOD-3 were up-regulated, and the pro-apoptotic caspase-6 was down-regulated. In the SV, SOD-2 increased, and the caspases-2, -3, -6 decreased. Hypoxia induced changes of only two genes as compared to the normoxic cultures. The expression of caspase-6 increased in the OC, whereas the expression of SOD-2 increased in the MOD and decreased in the SV.

Conclusions: We have shown that various culture conditions induce different expression pattern of apoptosis-related genes in the organotypic cochlear cultures as compared to freshly isolated tissues. This transcriptional pattern may reflect the survival ability of specific tissues and could become a tempting target for a pharmacological intervention in selected inner ear diseases.