Purchase this article with an account.
Ying Chau, Wai-Leung Suen, Jun Jiang, Yan Zeng, Jianan Qu; Mechanism of ultrasound-mediated transscleral delivery: temporary alteration of scleral structure increases permeability of macromolecules. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1071.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have proposed the use of low frequency ultrasound as a non-invasive approach to modulate the ocular barriers for transscleral drug delivery to the posterior segment of the eye. Using this approach, we observed significantly enhanced delivery in vivo. We hypothesize that ultrasound increases the porosity of scleral fiber network to allow improved diffusion of macromolecules. Here, we aim to understand the effect of ultrasound on sclera, the first barrier in the transscleral route of delivery.
The penetration of FITC-dextran of 70kDa through rabbit sclera was measured ex vivo with and without ultrasound. Sonication was applied directly above sclera at pre-designated frequency and intensity. Diffusivity was calculated by fitting the penetration profile, obtained by fluorescent microscopy of cryosectioned sclera, with 1-D diffusion equation. The collagen network structure of sclera was visualized dye-free using two-photon excitation microscopy (TPEM). Pore size of sclera was estimated by Renkin’s restricted diffusion model and textual analysis of TPEM images.
Dextran penetrated deeper into ultrasound-treated sclera, confirming that the barrier function of the sclera was weakened by sonication (Figure 1a). The transscleral penetration distance increases with decreasing frequency, suggesting the role of cavitation. Diffusivity of dextran increased up to 8 times in sclera after low frequency sonication. The enhancement was temporary, with the scleral permeability restored in 3 hours (Figure 1b). TPEM image revealed that ultrasound disrupted the ordered alignment of collagen and increased the scleral pore size (Figure 2), agreeing with the prediction by Renkin’s model.
Low frequency ultrasound alters the collagen network structure of sclera to increase the porosity, thereby enhancing the diffusion of macromolecules through the outmost barrier in the transscleral route of delivery.
This PDF is available to Subscribers Only