Ultrasound has recently been systematically studied to enhance trans-scleral drug delivery. Ultrasound-mediated trans-scleral drug delivery offers a novel alternative for treating posterior eye diseases including age-related macular degeneration. However, the effect that ultrasound exerts on sclera, as well as the potential mechanisms underlying the ultrasound-enhanced penetration of small molecules is still unknown. In this project, we first investigated the effect that ultrasound has on rabbit sclera using SHG&TPEF imaging. Both in-vitro and ex-vivo experiments were done, and the effect of ultrasound with different mechanical index (MI=0.03, 0.136, 0.2, 0.8) was investigated. To analyze the images, four quantitative methods were developed, and the results showed that the colla...[ Read more ]

Ultrasound has recently been systematically studied to enhance trans-scleral drug delivery. Ultrasound-mediated trans-scleral drug delivery offers a novel alternative for treating posterior eye diseases including age-related macular degeneration. However, the effect that ultrasound exerts on sclera, as well as the potential mechanisms underlying the ultrasound-enhanced penetration of small molecules is still unknown. In this project, we first investigated the effect that ultrasound has on rabbit sclera using SHG&TPEF imaging. Both in-vitro and ex-vivo experiments were done, and the effect of ultrasound with different mechanical index (MI=0.03, 0.136, 0.2, 0.8) was investigated. To analyze the images, four quantitative methods were developed, and the results showed that the collagen network structure did not shown significant change after ultrasound is applied. Next, we explored the diffusion of FITC-Dextran molecules using SHG&TPEF imaging, and concluded that the molecules tended to aggregate in the gaps between collagen fibrils, which suggested that the interfibrillar substances might play an important role in the trans-scleral penetration of molecules. Finally, we studied the diffusion profile of FITC-Dextran using a cryosectioning method, and found that the permeability of sclera was not homogeneous from the transverse view.