Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Scheie Eye Institute and F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2470-2477. doi: 10.1167/iovs.18-24096.
Intranasally delivered ST266, the biological, proteinaceous secretome of amnion-derived multipotent progenitor cells, reduces retinal ganglion cell (RGC) loss, optic nerve inflammation, and demyelination in experimental optic neuritis. This unique therapy and novel administration route delivers numerous cytokines and growth factors to the eye and optic nerve, suggesting a potential to also treat other optic neuropathies. Thus, ST266-mediated neuroprotection was examined following traumatic optic nerve injury.
Optic nerve crush injury was surgically induced in C57BL/6J mice. Mice were treated daily with intranasal PBS or ST266. RGC function was assessed by optokinetic responses (OKRs), RGCs were counted, and optic nerve sections were stained with luxol fast blue and anti-neurofilament antibodies to assess myelin and RGC axon damage.
Intranasal ST266 administered daily for 5 days, beginning at the time that a 1-second optic nerve crush was performed, significantly attenuated OKR decreases. Furthermore, ST266 treatment reduced damage to RGC axons and myelin within optic nerves, and blocked RGC loss. Following a 4-second optic nerve crush, intranasal ST266 increased RGC survival and showed a trend toward reduced RGC axon and myelin damage. Ten days following optic nerve crush, ST266 prevented myelin damage, while also inducing a trend toward increased RGC survival and visual function.
ST266 significantly attenuates traumatic optic neuropathy. Neuroprotective effects of this unique combination of biologic molecules observed here and previously in optic neuritis suggest potential broad application for preventing neuronal damage in multiple optic nerve disorders. Furthermore, results support intranasal delivery as a novel, noninvasive therapeutic modality for eyes and optic nerves.
鼻腔内给药的 ST266 是羊膜来源多能祖细胞的生物蛋白质分泌组，可减少实验性视神经炎中的视网膜神经节细胞（RGC）丢失、视神经炎症和脱髓鞘。这种独特的治疗方法和新的给药途径将许多细胞因子和生长因子递送至眼睛和视神经，表明其有潜力治疗其他视神经病变。因此，研究了 ST266 介导的神经保护作用在创伤性视神经损伤后的情况。
通过手术诱导 C57BL/6J 小鼠视神经挤压伤。每天用鼻腔内 PBS 或 ST266 处理小鼠。通过视动反应（OKR）评估 RGC 功能，计数 RGC，并使用卢索快速蓝和抗神经丝抗体对视神经切片进行染色，以评估髓鞘和 RGC 轴突损伤。
从进行 1 秒视神经挤压的时间开始，每天鼻腔内给予 ST266 治疗 5 天，可显著减轻 OKR 的下降。此外，ST266 治疗可减轻视神经内 RGC 轴突和髓鞘的损伤，并阻止 RGC 丢失。在进行 4 秒视神经挤压后，鼻腔内给予 ST266 可增加 RGC 存活率，并显示出减轻 RGC 轴突和髓鞘损伤的趋势。视神经挤压后 10 天，ST266 可防止髓鞘损伤，同时也显示出增加 RGC 存活和视觉功能的趋势。
ST266 显著减轻创伤性视神经病变。先前在视神经炎中观察到的这种独特的生物分子组合的神经保护作用表明，它有潜力预防多种视神经疾病中的神经元损伤。此外，这些结果支持鼻腔内给药作为治疗眼睛和视神经的新型非侵入性治疗方法。
