Effects of Furosemide Applied Chronically to the Round Window: A Model of Metabolic Presbyacusis

Hearing thresholds in elderly humans without a history of noise exposure commonly show a profile of a flat loss at low frequencies coupled with a loss that increases with frequency above ∼2 kHz. This profile and the relatively robust distortion product otoacoustic emissions that are found in elderly subjects challenge the common belief that age-related hearing loss (presbyacusis) is based primarily on sensory-cell disorders. Here, we examine a model of presbyacusis wherein the endocochlear potential (EP) is reduced by means of furosemide applied chronically to one cochlea of a young gerbil. The model results in an EP that is reduced from 90 to ∼60 mV, a value often seen in quiet-aged gerbils, with no concomitant loss of hair cells. Resulting measures of cochlear and neural function are quantitatively similar to those seen in aging gerbils and humans, e.g., a flat threshold loss at low frequencies with a high-frequency roll-off of approximately −8.4 dB/octave. The effect of the EP on neural thresholds can be parsimoniously explained by the known gain characteristics of the cochlear amplifier as a function of cochlear location: in the apex, amplification is limited to ∼20 dB, whereas in the base, the gain can be as high as 60 dB. At high frequencies, amplification is directly proportional to the EP on an ∼1 dB/mV basis. This model suggests that the primary factor in true age-related hearing loss is an energy-starved cochlear amplifier that results in a specific audiogram profile.