Abstract:
Traumatic optic neuropathy (TON) is a condition in which acute injury to the optic nerve from direct or indirect trauma results in vision loss. The most common cause of TON is indirect injury to the optic nerve caused by concussive forces that are transmitted to the optic nerve. TON occurs in up to 5% of closed-head trauma patients and there is currently no known effective treatment. One potential treatment option for TON is ST266, a cell-free biological solution containing the secretome of amnion-derived multipotent progenitor (AMP) cells. We investigated the efficacy of intranasal ST266 in a mouse model of TON induced by blunt head trauma. Injured mice treated with a 10-day regimen of ST266 showed an improvement in spatial memory and learning, a significant preservation of retinal ganglion cells, and a decrease in neuropathological markers in the optic nerve, optic tract, and dorsal lateral geniculate nucleus. ST266 treatment effectively downregulated the NLRP3 inflammasome-mediated neuroinflammation pathway after blunt trauma. Overall, treatment with ST266 was shown to improve functional and pathological outcomes in a mouse model of TON, warranting future exploration of ST266 as a cell-free therapeutic candidate for testing in all optic neuropathies.
摘要:
外伤性视神经病变(TON)是直接或间接创伤对视神经的急性损伤导致视力丧失的病症。TON的最常见原因是由传递到视神经的震荡力引起的对视神经的间接损伤。TON发生在多达5%的闭合性头部创伤患者中,并且目前没有已知的有效治疗。TON的一种潜在治疗选择是ST266,一种含有羊膜来源的多能祖细胞(AMP)分泌组的无细胞生物溶液。我们研究了鼻内ST266在钝性头部创伤诱导的TON小鼠模型中的功效。用ST266的10天方案治疗的受伤小鼠显示出空间记忆和学习的改善,保留了大量的视网膜神经节细胞,视神经的神经病理学标记物减少,视神经束,和背侧外侧膝状核。ST266治疗在钝性创伤后有效下调NLRP3炎性体介导的神经炎症途径。总的来说,用ST266治疗可改善TON小鼠模型的功能和病理结果,保证将来探索ST266作为所有视神经病变的无细胞治疗候选药物。