Translational Study on Neuroprotective Role of Conjuctivally Applied Nerve Growth Factor in Childhood Optic Gliomas (RF-2009-1536140)

In children, several neoplastic diseases, such as craniopharyngiomas and optic gliomas (OGs), can compromise visual function involving both anterior or retro-chiasmatic optic pathways. No specific therapy is currently available for OG-induced visual loss. Therefore, any improvement that might be obtained is of major clinical and socio-economical value both for patients and their relatives. Nerve growth factor (NGF) is a neurotrophin involved in the development and survival of sympathetic, sensory, and forebrain cholinergic neurons. In experimental animal models, NGF promotes nerve terminal outgrowth and neuron recovery after inflammatory, ischemic and toxic injuries. Exogenous NGF showed neuroprotective effects also on the visual system due to the presence of NGF receptors on the conjunctiva, cornea, as well as in the retinal ganglion cells (RGCs). In experimental animal models, intraocular NGF administration keeps RGCs from degeneration after optic nerve transection and ocular ischemia, and leads to the rescue of axotomized forebrain cholinergic neurons, while conjuctivally applied NGF proved to be effective in patients with corneal ulcers and severe glaucoma. Indeed, it has been reported that NGF, administered to the conjunctiva, reaches rapidly the retina and the optic nerve where this neurotrophin exerts its biological activities through the uptake by RGCs. Based on these evidences, the aim of this project is to evaluate the neuroprotective effects of NGF eye drops administration in optic nerve function of children with advanced optic pathways damage induced by OGs, as well as in an animal model of genetically engineered mice with knock-out of the NF-1 gene, developing gliomas of the optic pathways.

This project is carried out in collaboration with the Department of Pediatrics and Division of Pediatric Oncology at University Hospital "Agostino Gemelli", Catholic University of Sacred Heart, Rome Italy.

Falsini B, Chiaretti A, Rizzo D, Piccardi M, Ruggiero A, Manni L, Soligo M,
Dickmann A, Federici M, Salerni A, Timelli L, Guglielmi G, Lazzareschi I,
Caldarelli M, Galli-Resta L, Colosimo C, Riccardi R. Nerve growth factor improves
visual loss in childhood optic gliomas: a randomized, double-blind, phase II
clinical trial. Brain. 2016 Feb;139(Pt 2):404-14.