Decreased cochlear DNA receptor staining in MRL.MpJ-Fas(lpr) autoimmune mice with hearing loss

Objectives: Previous studies of decreased cochlear DNA binding in autoimmun e mice suggested that antibodies against a cochlear cell surface DNA recept or cause autoimmune hearing loss. However, the presence of a cochlear DNA r eceptor has not been determined. Therefore, immunohistochemistry with an an ti-DNA receptor antibody was performed on MRL.MpJ-Fas(lpr) (MRL/lpr) autoim mune mice to determine 1) which inner ear structures contain DNA receptors and 2) whether the receptor staining pattern changes as autoimmune disease progresses and hearing thresholds increase. Study Design: A prospective stu dy of the progression of hearing loss in autoimmune mice and correlated alt erations in immunostaining for the inner ear DNA receptor. Methods: One gro up of MRL/lpr mice (n = 10) was allowed to develop autoimmune disease, and auditory brainstem response (ABR) audiometry was performed at 4, 6, and 9 m onths of age to measure the progression of hearing loss. A second group (n = 5) was tested for ABR thresholds at 2 months of age and immediately bille d to assess receptor staining before the onset of autoimmune disease and he aring loss. The inner ears from all mice were immunohistochemically stained with an anti-DNA receptor antibody, and a qualitative analysis of the stai ning of cochlear structures was performed. Results: Auditory brainstem resp onse audiometry revealed a significant 20- to 30-dB elevation of thresholds as systemic disease progressed. Anti-DNA receptor staining was heaviest in the spiral Ligament and less intense in the spiral ganglion and cochlear n erve. Both groups showed a similar pattern of staining in these structures. The stria vascularis and hair cells also stained in both groups. However, the stria cells of normal-hearing mice showed diffuse intracellular immunor eactivity, whereas older mice displayed less staining that was confined to the cell membranes. Conclusions: The inner ears of MRL/lpr mice contain DNA receptors, Autoimmune hearing loss was correlated with weaker overall intr acellular staining in the stria vascularis and hair cells but increased sta ining of the cell membranes. This suggested DNA receptors have impaired end ocytosis and more receptors remain on the cell membrane, possibly as a resu lt of binding by circulating autoantibodies.