NERVE GROWTH FACTOR (NGF) INTRANASAL TREATMENT IN OPTIC NERVE CRUSH (ONC) RAT MODEL

Optic nerve crush (ONC) has been extensively described in rodents and used as a model of retina degenerative pathologies and regenerative processes in the central nervous system. Because the neuro-retina (Retinal Ganglion Cells - RGCs) depends on neurotrophic factors, including the Nerve Growth Factor (NGF), this study uses ONC as a model to investigate the effects of the NGF intranasal treatment following axonal degeneration. Different time-points were chosen to investigate the neuro-protective/neuro-regenerative effects of intranasal treatment with different NGF doses by analysing the distribution and co-localisation of specific RGC and axonal markers for neuronal growth and synaptic plasticity, as well as the potential apoptotic activation. Further, the functional activity and its potential recovery were assessed by electroretinography tests at the same time-points. Based on the electrophysiological results and confocal microscopy analysis, the present study demonstrated that the ONC model induces a progressive functional alteration of the retina post-crush that mainly involves the RGCs, induces an increased RGC apoptosis and a reduced presence of RGC able to regenerate. The intranasal NGF administrations during the critical post ONC period of two weeks or three weeks, induce a dose regimen-dependent functional and structural recovery of ONC-induced retinal damage. It is worth to note that the intranasal treatment acts on the central nervous system. Thus, retinal recovery may be sustained by a multifaceted mechanism integrating increased local NGF availability with the retrograde transport of factors, including neurotrophins, from central visual areas.