Recent findings and emerging questions in cochlear noise injury.

The lives of an estimated 10 million people in the United States are impacted by debilitating cochlear noise injury acquired in leisure or occupational settings (Kopke et al., 2007). Although noise injury has been intensively studied for decades, the only clinically successful preventive measure against noise-induced hearing loss (NIHL) remains a hearing protective device (HPD), and the only treatment is a hearing aid. We cannot yet identify people who are most at risk in noisy environments. Even if we could, there is still no practical pharmacological approach to minimizing hearing loss. HPD use is often uneven and impractical in many settings, and HPD effectiveness is simply not up to the task in some work environments. A continued broad and well-funded assault on gaps in our understanding of NIHL remains vital. Significant discoveries can emerge from studies aimed at seemingly remote facets of noise injury, and narrowly defining which facets merit study will always be a mistake. Here we briefly review recent progress in several areas. Particularly exciting recent developments include new evidence for a phagocytic function of supporting cells in removing damaged outer hair cells (OHCs), demonstration of large scale inflammatory cell invasion of the lateral wall after noise, support for strong genetic modulation of injury to the lateral wall, and the discovery of remarkable interactions between noise and age of exposure. We also update the potential role in NIHL of the cochlear lateral wall in light of newly discovered functions of gap junctions. Other recent reviews (Darrat et al., 2007; Hawkins et al., 2005; Henderson et al., 2006; Hibino et al., 2006; Kopke et al., 2007; Le Prell et al., 2007b; Ohlemiller, 2006; Talaska et al., 2007; Wangemann, 2006) offer more comprehensive accounts of findings touched upon here. Most recent studies of noise injury have utilized mouse models. Mice are the best model for questions that are overtly genetic, and have distinct advantages for aging studies, yet they may pose limitations for physiologic and biochemical studies. Many strains exhibit pronounced vulnerability to NIHL (e.g., Ohlemiller et al., 2000a), but still may show less hair cell loss in the exposure band than guinea pigs or chinchillas (Ou et al., 2000; Wang et al., 2002b). Mice also remain subject to concerns about the comparability of mechanisms for hearing in the audiologic and ultrasonic range. Two increasingly recognized phenomena add caveats to the touted high degree of genetic control of mouse models. First is environmentally-modulated epigenetic control of transcription and translation, which can effectively alter genotype by permanently silencing genes (see below). Second is variation in the number of copies of genes, which occurs even within inbred strains such as C57BL/6 (B6) (Watkins-Chow et al., 2008). Copy number variation is thought to arise from faulty DNA repair, and can alter phenotype via gene-dose effects. Depending on how early it occurs in development, it may render most individuals chimeric for many genes. Copy number variation may require presently non-standard tests to account for some differences among nominally genetically identical mice.