■靶向药物递送到视神经乳头可能在视神经病变的临床前研究和后期临床管理中有用,然而,没有FDA批准的药物递送系统来实现这一目标。这项工作的目的是开发一种视神经乳头给药技术。
■研究了接近视神经头的不同策略,包括标准的玻璃体内注射和眶后注射。通过创建巩膜切开术并将导管引入脉络膜上腔来优化新型脉络膜到光学神经(SCONE)递送。在直接可视化下,导管被引导至视神经头。印度墨水被注入。在新西兰白兔眼(总共25只动物)中进行脉络膜上入路。参数,包括微针的尺寸和设计,导管设计,和导管尖端角度,进行了离体和体内优化。
■在候选视神经头方法中,玻璃体内,眶后,脉络膜上入路能够将印度墨水定位在视神经2毫米以内。进一步研究了脉络膜上入路,优化后,能够在高达80%的尝试中将印度墨水直接沉积在视神经头内。在成功交付SCONE的眼中,视觉诱发电位的潜伏期和振幅与未治疗的眼睛没有差异。
■SCONE递送可用于靶向药物递送至兔的视神经头,而在解剖学或功能上没有可测量的毒性。该系统的成功开发可能为在动物模型中研究视神经头特异性药物递送提供新的机会。和治疗视神经病变的范式转换管理策略。
■在这里,我们展示了一种用于靶向递送到视神经头的新方法的数据,解决视神经疾病治疗中尚未满足的重大需求。
UNASSIGNED: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique.
UNASSIGNED: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo.
UNASSIGNED: Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye.
UNASSIGNED: SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies.
UNASSIGNED: Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies.