STRC Research

Round Window Membrane Permeability to Solutes — Salt & Ma 2001

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Round Window Membrane Permeability — Salt & Ma 2001

Citation: Salt, A.N. & Ma, Y. (2001). Quantification of solute entry into cochlear perilymph through the round window membrane. Hearing Research, 154(1-2), 88-97. DOI: 10.1016/S0378-5955(01)00177-6

Authors: Alec N. Salt, Yilong Ma — Department of Otolaryngology, Washington University School of Medicine, St. Louis.

Key Claims

  1. Round window membrane permeability to TMPA (trimethylphenylammonium) measured at 1.9 × 10⁻⁸ cm/s — a concrete, usable number for drug delivery modeling.
  2. After 90 min of continuous round window irrigation with 2 mM TMPA, basal turn (1.4 mm from base) reaches 330 µM — 16.5% of the applied concentration.
  3. Second turn (7.5 mm from base) reaches only 15 µM average after 90 min — just 0.8% of applied dose.
  4. Steady-state concentration gradient persists even after 24 h of continuous application: apex remains ~40x lower than base. Prolonged application does not equalize distribution.
  5. Longitudinal perilymph flow rate: 4.4 nl/min base-to-apex. Low but skews apical delivery slightly.
  6. Clearance half-time from scala tympani: ~60 min.
  7. Perforating the otic capsule immediately disrupts gradients — CSF rushes in through the cochlear aqueduct and displaces native perilymph rapidly. Sampling after perforation is meaningless.
  8. Distribution is diffusion-dominated, not flow-dominated. Molecular size matters: small molecules spread further.

Methodology

  • Guinea pig model (n=8). Ion-selective microelectrodes sealed into scala tympani (turn I and II) without perilymph leakage.
  • Washington University Cochlear Fluids Simulator v1.4 (public domain) used to fit experimental curves.
  • Fitted three free parameters: RWM permeability, perilymph flow rate, and ST clearance half-time.

Figures Worth Remembering

  • Fig. 3: TMPA stays mostly confined to basal cochlea at 90 min.
  • Fig. 8: Even at 24 h, steep base-to-apex gradient remains. Cannot achieve uniform cochlear distribution by round window alone.
  • Table 1: All simulation parameters — permeability 1.9×10⁻⁸ cm/s, flow 4.4 nl/min, clearance t½ 60 min, RW area 1.164 mm².

Relevance to STRC / Gene Therapy

Round window injection is the standard route for AAV delivery to the inner ear (including Iranfar 2026 STRC dual-AAV paper). This paper quantifies exactly why basal hair cells get hit harder than apical ones — the basal turn sits at 330 µM while the apex sees <10 µM of the same dose. For STRC therapy targeting OHCs along the full cochlear length, this gradient is a real constraint. Strategies to improve apical delivery: cochleostomy, canalostomy, higher dose, or larger injection volume.

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