Degeneration of the stria vascularis in quiet-aged gerbils: Linking structural, cellular and molecular changes to cochlear function.

Presbycusis, or age-related hearing loss, is a prevalent condition characterized by progressive auditory decline, significantly impacting quality of life in older adults. While sensorineural damage has been widely studied, degeneration of the stria vascularis (SV) remains underexplored despite its essential role in cochlear ion homeostasis. The SV is organized into three cellular layers-marginal, intermediate, and basal cells-each with distinct functions critical for maintaining the endocochlear potential. Using the quiet-aged Mongolian gerbil-a well-established model of metabolic presbycusis-we systematically mapped the structural and cellular degeneration of the SV and linked these changes to cochlear function. We assessed cochlear function using auditory brainstem response (ABR) measurements and quantified age-related atrophy of the strial cell layers using immunofluorescence, confocal microscopy, and 3D reconstruction. We identified a striking, region-specific pattern of degeneration, with the greatest atrophy occurring in ATP1A1-expressing marginal cells, followed by KCNJ10-expressing intermediate cells, and comparatively little atrophy in CLDN11-expressing basal cells. Notably, atrophy was most pronounced in the cochlear apex and base, regions critical for low- and high-frequency hearing. We further established a significant correlation between the decline in cochlear function and the extent of atrophy of the individual strial cell layers, especially in the cochlear base. By moving beyond traditional cross-sectional assessments of age-related degeneration of the SV, this work provides a more nuanced understanding of how strial pathology contributes to age-related decline in cochlear function and may inform therapeutic interventions targeting strial function to mitigate age-related hearing loss even when sensorineural function is compromised.