Effects of NGF-chitosan on alleviating secondary degeneration and repairing primary degeneration after expanded partial optic nerve transection

Optic neuropathy is one of the main causes of irreversible blindness in the world, and there is no effective treatment in clinic. Both primary degeneration and secondary degeneration play an important role in the injury caused by optic neuropathy. Partial optic nerve transection (PONT) model can be used to study these two kinds of degeneration simultaneously. However, there is currently no measure that can effectively intervene in both types of injuries concurrently. Here, we constructed an expanded partial optic nerve transection (EPONT) model. Nerve growth factor (NGF)-chitosan locally implanted into the injured area could simultaneously intervene in the secondary and primary degeneration, not only protecting the ventral part of the injured optic nerve, but also promoting the regeneration of the dorsal part. Visual functions, including pupillary light reflex and depth perception, were also well preserved. NGF-chitosan exerted biological effects by enhancing the expression of NGF and tyrosine kinase A (TrkA) in the optic nerve and retinal ganglion cells (RGCs). Furthermore, NGF-chitosan played a protective and repairing role by inhibiting the activation of microglia in the ventral area of the injured optic nerve and increasing the expression of mammalian target of rapamycin (mTOR) in RGCs. Our results demonstrate that the local use of NGF-chitosan in the injured area effectively repaired the optic nerve, which provides a new measure for the clinical treatment of optic nerve injury.