Neurotrophins are a family of
proteins that support neuronal proliferation, survival, and differentiation in the central and peripheral nervous systems, and are regulators of neuronal plasticity.
Nerve growth factor is one of the best-described
neurotrophins and has advanced to clinical trials for treatment of ocular and
brain diseases due to its trophic and regenerative properties. Prior trials over the past few decades have produced conflicting results, which have principally been ascribed to adverse effects of systemic
nerve growth factor administration, together with poor penetrance of the blood-brain barrier that impairs
drug delivery. Contrastingly, recent studies have revealed that topical ocular and intranasal
nerve growth factor administration are safe and effective, suggesting that topical
nerve growth factor delivery is a potential alternative to both systemic and invasive intracerebral delivery. The
therapeutic effects of local
nerve growth factor delivery have been extensively investigated for different ophthalmic diseases, including neurotrophic
keratitis,
glaucoma,
retinitis pigmentosa, and
dry eye disease. Further, promising pharmacologic effects were reported in an
optic glioma model, which indicated that topically administered
nerve growth factor diffused far beyond where it was topically applied. These findings support the therapeutic potential of delivering topical
nerve growth factor preparations intranasally for acquired and degenerative
brain disorders. Preliminary clinical findings in both traumatic and non-traumatic acquired
brain injuries are encouraging, especially in pediatric patients, and clinical trials are ongoing. The present review will focus on the
therapeutic effects of both ocular and intranasal
nerve growth factor delivery for diseases of the brain and eye.