Prophylactic treatment with amnion progenitor cell secretome mitigates traumatic optic neuropathy.

Traumatic optic neuropathy (TON), often resulting from repetitive mild traumatic brain injury (r-mTBI), is a major contributor to irreversible visual impairment, with few preventive therapeutic options available. This study evaluates the prophylactic efficacy of ST266, a biologically active secretome derived from amnion epithelial cells, in mitigating TON-related visual and cognitive dysfunction in a murine model of r-mTBI. Mice received five closed-head injuries spaced 48 h apart, preceded by intranasal delivery of ST266 starting 24 h before the first injury and administered twice daily for ten days. Behavioral performance was assessed using the Barnes Maze and optomotor response (OMR). Pathological and biochemical analyses were conducted on the eye and optic nerve tissues. Prophylactic treatment with ST266 preserved retinal ganglion cell (RGC) count, significantly attenuated optic nerve inflammation, and reduced microgliosis, TLR4, and NLRP3 expression in the intracanalicular segment of the optic nerve. ST266 protected spatial learning in the Barnes Maze during the acquisition phase but did not improve memory retention or visual function by OMR. Importantly, this model reflects translationally relevant features of human TON, such as RGC degeneration and visual-cognitive impairments. Our findings identify ST266 as a potential prophylactic therapy for TON, especially in populations at elevated risk (e.g., athletes, military personnel, or individuals prone to falls). Its non-invasive intranasal administration, established safety profile, and anti-inflammatory and neuroprotective effects make it a viable candidate for clinical translation. This is the first study to demonstrate protection against optic nerve injury before trauma onset, addressing a critical unmet need in neuro-ophthalmology.