Figure 2.

AAV8-Whirlin Gene Therapy Restores Stereocilia Length in Whirler Utricles

(A) Stereocilia length measurements of utricular hair cells. The “normal control” group includes data from wild-type and heterozygous littermates (whrn^+/+ and whrn^+/wi, n = 4). The “whirler untreated control” group includes data from whirler mice (whrn^wi/wi) that did not receive AAV8-whirlin gene therapy (n = 5). The “whirler w/ AAV8-whirlin” group includes data from all whirler ears (whrn^wi/wi) that received AAV8-whirlin gene therapy, including ones with low or no infection (n = 28). The “AAV8-whirlin contralateral” group includes data from the contralateral whirler ears (whrn^wi/wi) that did not receive AAV8-whirlin gene therapy (n = 28). The “>40% infection” group includes data from whirlers with >40% AAV8-whirlin infection in utricular hair cells (n = 18). The “>40% contralateral” group includes data from the contralateral whirler ears that did not receive AAV8-whirlin gene therapy in the >40% infection group (n = 18). The “whirler w/ AAV8-GFP” group includes data from whirlers that received AAV8-GFP as a sham surgery control. All stereocilia length measurements were made using confocal images with 3D rendering. Error bars represent SEs. *p < 0.05, ***p < 0.001. (B) Scanning electron microscopy images showing whirler untreated control (whrn^wi/wi, no gene therapy) vestibular hair cells that have aberrantly short stereocilia bundles (top panel), and whirler vestibular hair cells with elongated stereocilia bundles after AAV8-whirlin gene therapy (bottom panel). Examples of stereocilia length are shown with red brackets. (C) There was a strong positive correlation (R² = 0.67) between utricular hair cell infection efficiency and stereocilia length.