You Shuqi, Zhou Hongsheng, Yang Shicheng, Wu Suqian, Chen Xiangwu, Zhang Rong, Chen Wei, Wang Huan, Mo Xiaofen
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.
J Ocul Pharmacol Ther. 2023 Mar;39(2):175-184. doi: 10.1089/jop.2022.0114.
To investigate the efficacy and safety of pulsed ultrasound (PUS) in enhancing fluorescein sodium (NaF) transport to the rabbit eye through the transscleral and transconjunctival routes . PUS and NaF were applied onto the supratemporal sclera/conjunctiva of healthy rabbit eyes. PUS (1 MHz, 2.37 W/cm, 30% duty cycle, 5-min application time) was performed 3 times with a 5-min interval. In the same process, NaF was administered to the eye without PUS in the control. NaF concentrations in the vitreous and retina-choroid were determined by fluorescence measurement. The safety of PUS application was assessed based on temperature and intraocular pressure measurements, clinical observations, electroretinography, histology, and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay. In comparison to the control, higher NaF concentrations were found in the retina-choroid following transscleral (2.45-fold) and transconjunctival (2.97-fold) PUS applications ( < 0.05). NaF concentrations in the vitreous were 3.15 and 5.86 times greater in transscleral and transconjunctival PUS applications, respectively, compared with those obtained without PUS application ( < 0.05), and NaF level in the vitreous after transconjunctival PUS application was 2.61 times that of transscleral PUS application ( < 0.05). Ocular findings were transient and mild conjunctival injection, with no other structural and functional changes in PUS-treated eyes. PUS treatment can improve transscleral and transconjunctival delivery of NaF efficiently and safely. Transscleral and transconjunctival PUS applications offer potential clinical benefit in increasing drug penetration to the posterior segments of the eye for the noninvasive treatment of ocular diseases.
研究脉冲超声（PUS）通过经巩膜和经结膜途径增强荧光素钠（NaF）向兔眼转运的有效性和安全性。将PUS和NaF应用于健康兔眼的颞上巩膜/结膜。PUS（1MHz，2.37W/cm，30%占空比，5分钟施加时间）进行3次，间隔5分钟。在同一过程中，对照组在未进行PUS的情况下对眼睛给予NaF。通过荧光测量确定玻璃体和视网膜脉络膜中的NaF浓度。基于温度和眼压测量、临床观察、视网膜电图、组织学以及末端脱氧核苷酸转移酶dUTP缺口末端标记试验评估PUS应用的安全性。与对照组相比，经巩膜（2.45倍）和经结膜（2.97倍）应用PUS后，视网膜脉络膜中的NaF浓度更高（P<0.05）。与未应用PUS相比，经巩膜和经结膜应用PUS后玻璃体中的NaF浓度分别高3.15倍和5.86倍（P<0.05），经结膜应用PUS后玻璃体中的NaF水平是经巩膜应用PUS的2.61倍（P<0.05）。眼部表现为短暂且轻微的结膜充血，PUS治疗的眼睛没有其他结构和功能变化。PUS治疗可以有效且安全地改善NaF的经巩膜和经结膜递送。经巩膜和经结膜应用PUS在增加药物向眼后段渗透以无创治疗眼部疾病方面具有潜在的临床益处。
