Targeted Delivery of Microneurotrophin <scp>BNN27</scp> via Biomaterial Grafts Protects Retinal Ganglion Cells After Optic Nerve Injury

Emerging neurotrophin treatments for optic nerve injury (ONI) aim to prevent the loss of retinal ganglion cells (RGCs) and enhance axonal regeneration. Microneurotrophins (MNTs), small-molecule mimetics of neurotrophins, have shown neuroprotective effects in various animal models of neurodegeneration, yet MNT effects on ONI remain unknown. Here, we study the effects of BNN27, a MNT that mimics NGF, in a mouse model of optic nerve crush (ONC) and compare the targeted administration via biomaterial grafts placed around the ONC lesion against standard eye drop delivery. Compared to eye drop delivery, targeted biomaterial-based BNN27 delivery resulted in more consistent and efficient RGC neuroprotection and reduced microglia-mediated inflammation in the ONC lesion. Our findings demonstrate that targeted delivery of MNTs can alleviate key consequences of ONI and, therefore, be an essential part of effective combinatorial ONI treatments.