光介导超声技术（PUT）抗眼底新生血管作用的可行性分析及系统优化研究

Anti-angiogenic therapy represents a main strategy to treat retinal neovascularizaiton. Whereas anti-angiogenic strategies such as anti-VEGF drugs, laser photocoagulation, and photodynamic therapy have proven their clinical efficiency, they carry limitations like invasive property, retinal degeneration and atrophy, and economic burden. We developed, for the first time, a novel, noninvasive anti-microvascular therapy that we call photo-mediated ultrasound therapy (PUT). PUT applies synchronized laser pulses and ultrasound bursts on target vessels. The technique is based on controlled induction and promotion of micro-cavitation activity in the target vessels. In a chicken yolk sac membrane model and a rabbit ear mode, we have demonstrated that PUT: 1, is a noninvasive method without requiring either photosensitizer or microbubbles; 2, employs ultrasound and laser pulses under safety limit; and 3, has high-selectivity since specific wavelength(s) enables the best optical absorption contrast of hemoglobin over other chromophores, and cavitation is limited to blood vessels, leaving the surrounding tissue intact. In consideration of the high penetration of photo and ultrasound in eye, we have built a retina-targeted PUT system and further, in vivo, verified the high-selectivity and safety on three rabbit eyes. Based on our previous encouraging work, we aim to elucidate the underlying mechanism of PUT—cavitation—thrombus pathway, optimize the parameters specifically for angiogenesis, and explore the feasibility of PUT in the treatment of retinal angiogenesis. All the work would provide solid theoretical basis for future translational application of PUT in retinal diseases.

抑制新生血管是治疗新生血管性眼底病的主要手段。目前临床上多采用抗VEGF药物、激光光凝、光动力疗法，但它们有侵入性、视网膜变性萎缩、价格高昂等缺点。光介导超声疗法（PUT）是我们自主开发的，采用同步发生的激光与超声，以诱导血管内微泡空穴效应为机制的新型抗血管方法。我们前期动物微血管模型证明PUT具有：1非侵入性：无需注射光敏剂或微泡；2安全性：采用安全阈值下的激光、超声能量；3高选择性：血红蛋白对特定波长光吸收能力高；空穴效应局限于血管内，故PUT对周围组织无损伤。鉴于光、声的眼器官穿透优越性，我们进一步搭建了治疗兔眼底血管的PUT系统，并且在3只兔眼上佐证了PUT的高选择性与安全性。本研究拟在前期工作基础上，通过体外血管模型和动物模型，进一步揭示“PUT-空穴-血栓形成”的治疗机制；优化针对新生血管的PUT技术参数；探讨PUT治疗眼底新生血管的可行性，为PUT的临床转化奠定理论和实践基础

光介导超声疗法（PUT）是我们前期自主开发的，采用同步发生的激光与超声，以诱导血管内微泡空穴效应为机制的新型抗血管方法。本项目在国自然项目（81770973）的支撑下，构建了兔眼角膜新生血管、视网膜新生血管模型，验证PUT治疗兔眼角膜新生血管有效，并优化相关参数；进一步设计并搭建了一套集治疗超声、PAM和OCT于一体的多模态成像治疗系统；开发了集成的光声感应和PUT系统，以研究使用激光系统和超声换能器进行光声信号实时感应和PUT治疗的可行性。本项目的开展为PUT的临床转化奠定理论和实践基础。