Sensorineural hearing loss is often associated with degeneration of the vasculature in the stria vascularis, a vascularized epithelium in the lateral wall of the cochlea required for hearing function. The mechanism for strial atrophy remains elusive, however, and no curative or preventative interventions exist. This research tests two predictions of the hypothesis that augmenting or ?normalizing? vascular function in the cochlea may slow or reverse atrophy in the stria vascularis: 1) that strial atrophy in affected mice is associated with vascular abnormalities and loss of vascular integrity in the stria vascularis and 2) that improved endothelial barrier function, vascular tone and angiogenesis protects mice against aminoglycoside-induced strial atrophy. To measure such changes, the approach uses innovative techniques to compare, in normal and injured inner ears, the morphology of vasculature including microvessels in the whole cochlea in 3D as well as the molecular makeup of the cochlear vasculature at the single cell level. Thus, in addition to testing the predictions above, this research could identify cell subtypes, molecular mechanisms and structures of potential significance to circulation and solute transport in the cochlea, which has broad implications for understanding and managing inner ear disease. !
CDC statistics indicate that hearing loss affects 2-3 per 1000 children born as well as an increasingly large fraction of seniors and veterans. The aim of the proposed research is to model a widespread degenerative process associated with aging, noise exposure and ototoxicity known as strial atrophy and to evaluate the role of vascular dysfunction in the progression of this process. Study of the fundamental processes that contribute to hearing loss and the innate protective mechanisms of the inner ear could identify therapeutic strategies to slow or reverse hearing loss.
