Animal models have definitively demonstrated that the immune response of the inner ear can lead to reversible or permanent damage to the delicate inner ear structures. One of the first animal models for AIED was developed by Beickert who immunized guinea pigs with homologous inner ear tissue. Although the guinea pigs developed cochlear lesions, hearing loss was not demonstrated and antibodies to inner ear antigens were not identified (24).
Yoo developed an animal model for AIED based on type II collagen. Rats were immunized with bovine type I and type II collagen. Rats immunized with type I collagen or with denatured collagen had no change in hearing, whereas rats immunized with type II collagen had hearing loss based on auditory brainstem recordings. High levels of antibodies to type II collagen were identified. Upon sacrifice, histologic findings were of cochlear nerve degeneration and perineural vasculitis (25).
Harris developed an animal model of AIED when he immunized guinea pigs with bovine inner ear antigen and found that the guinea pigs uniformly developed antibodies to the inner ear antigen in both their sera and perilymphatic fluids. Some of these animals (32%) developed hearing loss based on elevated cochlear action potentials. Interestingly, in the animals that developed hearing loss, roughly one-half had unilateral deficits only. When sacrificed, the animals with hearing loss had demonstrable loss of cochlear neurons, edema, hemorrhage, and a mononuclear cell infiltrate. The extent of these histopathologic changes was highly variable among the animals and was not correlated with the levels of antibodies found (26).
In 1991, Zajic et al. developed murine monoclonal antibodies against guinea pig cochlear epithelia. This was done by immunizing mice with inner ear homogenates extracted from guinea pigs. They identified three significant monoclonal antibodies: Kresge Hearing Research Institute (KHRI-1), an IgM antibody staining Hensen's cells; KHRI-2, an IgM antibody staining the tectorial membrane, spiral limbus, and Hensen' s cells; and KHRI-3, an IgG antibody staining the phalangeal processes of outer pillar cells and the apical portions of Deiter's cells. A Western blot of the KHRI-3 monoclonal antibody against inner ear tissue bound to proteins at 70 to 75 kDa and 68 to 70kDa. The KHRI-1 and KHRI-2 monoclonal antibodies did not bind to any proteins on Western blots (27). Subsequent experiments have taken KHRI-3 and infused it directly into the inner ears of guinea pigs via osmotic pumps. Half of these guinea pigs developed a 25 to 55 dB hearing loss. Control guinea pigs infused with irrelevant antibodies had no change in hearing (28). Further experiments have suggested that the inner ear antigen to which KHRI-3 monoclonal antibody is binding among the supporting cells is a choline transport protein, specifically, choline transporterlike protein-2 (CTL-2). These investigators suggest that CTL-2 is a possible target of autoimmune hearing loss in humans (29). Unfortunately, the KHRI-3 monoclonal antibody assay is not commercially available.
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