Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) refers to optic nerve damage caused by trauma, leading to partial or complete loss of vision. The primary treatment options, such as hormonal therapy and surgery, have limited efficacy. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), a functional endogenous neuroprotective peptide, has emerged as a promising therapeutic agent. In this study, we used rat retinal ganglion cell (RGC) exosomes as nanosized vesicles for the delivery of PACAP38 loaded via the exosomal anchor peptide CP05 (EXOPACAP38). EXOPACAP38 showed greater uptake efficiency in vitro and in vivo than PACAP38. The results showed that EXOPACAP38 significantly enhanced the RGC survival rate and retinal nerve fiber layer thickness in a rat TON model. Moreover, EXOPACAP38 significantly promoted axon regeneration and optic nerve function after injury. These findings indicate that EXOPACAP38 can be used as a treatment option and may have therapeutic implications for patients with TON.

创伤性视神经病变（TON）是指由创伤引起的视神经损伤，导致部分或完全视力丧失。主要的治疗选择，如激素治疗和手术，疗效有限。垂体腺苷酸环化酶激活多肽38（PACAP38）是一种具有功能的内源性神经保护肽，已成为一种有前景的治疗药物。在本研究中，我们使用大鼠视网膜神经节细胞（RGC）外泌体作为纳米级囊泡，通过外泌体锚定肽CP05负载PACAP38（EXOPACAP38）进行递送。EXOPACAP38在体外和体内的摄取效率均高于PACAP38。结果表明，在大鼠TON模型中，EXOPACAP38显著提高了RGC存活率和视网膜神经纤维层厚度。此外，EXOPACAP38显著促进了损伤后的轴突再生和视神经功能。这些发现表明，EXOPACAP38可作为一种治疗选择，可能对TON患者具有治疗意义。