Inflammation in the inner ear contributes to tissue damage in Pendred syndrome

Pendred syndrome, an autosomal‐recessive disorder characterized by deafness and goiter, is caused by a mutation of SLC26A4, which codes for the HCO 3 − transporter pendrin. We investigated the relationship between pendrin expression and deafness using adult mice that have (+/−) or lack (−/−) a complete Slc26a4 gene. Previously we reported that pendrin is expressed in the cochlear lateral wall and −/− mice have an acidified endolymphatic pH, a hyperpigmented stria with reorganized marginal cells and a loss of tissue mass in the spiral ligament. These data suggested that loss of pendrin alters tissue pH in the lateral wall and leads to tissue damage followed by cellular reorganization. Here we test the hypothesis that inflammation contributes to tissue damage. Microarray analysis was performed on RNA isolated from stria vascularis of +/+ and −/− mice. A group of transcripts was quantified by qRT‐PCR in RNA isolated from stria vascularis, spiral ligament, liver and spleen of 80 – 83 days old male +/− and −/− mice. Macrophage markers including Ptprc (=Cd45), Cd68, Cd83, Lysz, Lgals3 (= Mac‐2), Ms2, Ctsb, Ctss, Ctsk, C1r, C3 and C4 were significantly increased in stria vascularis of −/− mice compared to +/+ mice. No expression of markers of acute inflammation, T‐cells, NK cells, or B cells was found in stria vascularis of +/+ or −/− mice. Expression of Cd83, Lyzs and C3 in −/− mice was increased 4, 122 and >30‐fold in stria vascularis and 2, 9 and 7‐fold in spiral ligament compared to +/− mice. No difference in expression of Cd83, Lyzs and C3 was found in liver or spleen. The data suggest that inflammation contributes to tissue damage of stria vascularis and spiral ligament and that inflammation resolves with persistent macrophages remaining in stria vascularis. NIH‐R01‐DC01098, NIH‐P20‐ RR017686