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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 (EXO  PACAP38  ). EXO  PACAP38   showed greater uptake efficiency  in vitro  and  in vivo  than PACAP38. The results showed that EXO  PACAP38   significantly enhanced the RGC survival rate and retinal nerve fiber layer thickness in a rat TON model. Moreover, EXO  PACAP38   significantly promoted axon regeneration and optic nerve function after injury. These findings indicate that EXO  PACAP38   can be used as a treatment option and may have therapeutic implications for patients with TON.

frontiers in cell and developmental biology

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