Examination of Effects of Low-Frequency Ultrasound on Scleral Permeability and Collagen Network

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• 作者：Wai-Leung Langston Suen^&lowast ; ; Jun Jiang^&dagger ; ; Hoi Sang Wong^&lowast ; ; Jianan Qu^&dagger ; ; Ying Chau^&lowast ; ; ^&Dagger ; ; ^{ying.chau@ust.hk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Second harmonic generation imaging ; Drug delivery ; Mechanical index ; Texture analysis ; Collagen ; Scleral permeability
• 刊名：Ultrasound in Medicine & Biology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：42
• 期：11
• 页码：2650-2661
• 全文大小：1622 K

文摘

Delivery of therapeutics to the intraocular space or to targeted tissues in the posterior segment is challenging because of the structural and dynamic barriers surrounding the eye. Previously, we reported the feasibility of using ultrasound (US) irradiation to deliver macromolecules to the posterior segment of the eye via the transscleral route, which consists of sclera as the outermost anatomic barrier. In this study, we found that although ultrasound increases scleral permeability for macromolecules, the scleral collagen arrangement remains undisturbed. In an ex vivo experiment, protein permeation across the sclera was significantly enhanced by ultrasound in the stable cavitation regime. The scleral collagen network was further examined by second harmonic generation imaging. Quantitative image analysis techniques were adopted to examine the density, anisotropy and interlacing pattern of collagen fibers before and after ultrasound irradiation. Repeated ultrasound applications did not induce significant changes in the arrangement of collagen fibrils at 40 kHz with a spatial average temporal average intensity (I_SATA) <1.8 W/cm². These parameters correspond to a mechanical index (MI) below 0.8 in our setting. These data suggested that enhanced permeation of macromolecules across the sclera was achieved without disturbing the collagen network of the sclera. This evidence supports that low-frequency, low-intensity ultrasound is a tolerable approach to transscleral drug delivery.