Round Window Membrane Permeability
The round window membrane (RWM) is the main access point for delivering drugs and gene therapy vectors to the inner ear without surgery. It’s permeable but slow.
Salt & Ma 2001 measured it directly in guinea pigs. RWM permeability to TMPA: 1.9 × 10⁻⁸ cm/s. After 90 min of continuous irrigation, the basal turn (1.4 mm from base) reached 330 µM — 16.5% of the applied dose. The second turn (7.5 mm) reached just 15 µM — 0.8% of applied dose.
That gradient doesn’t go away with time. Simulating 24 h of continuous application: the apex remains 40× lower in concentration than the base. You can’t equilibrate the cochlea by prolonging round window exposure.
The physics: diffusion moves substance apically, clearance from scala tympani removes it (t½ ≈ 60 min). These two processes reach a steady state that always favors the base. Longitudinal perilymph flow (4.4 nl/min base-to-apex) is a minor contributor.
For STRC gene therapy: AAV delivered via round window injection hits basal OHCs much harder than apical ones. This is why basal cochlea typically shows better rescue in animal models. To reach apical turns — where lower-frequency hearing lives — you need higher dose, longer application, or an alternative access route (canalostomy, posterior semicircular canal injection).
Perforating the otic capsule immediately disrupts everything: CSF floods in through the cochlear aqueduct and washes out native perilymph gradients in minutes. Any fluid sampling after perforation is not measuring native perilymph.
Connections
[source]2001-salt-ma-hear-res-rwm-permeability[about]Cochlear Drug Delivery Gradients[applies]STRC Research Portal[see-also]OHC-Specific Gene Delivery[see-also]STRC Gene Therapy sphere