NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush

Abstract

Eye-drop recombinant human nerve growth factor (ed-rhNGF) has proved to recover the retina and optic nerve damage in animal models, including the unilateral optic nerve crush (ONC), and to improve visual acuity in humans. These data, associated with evidence that ed-rhNGF stimulates the brain derived neurotrophic factor (BDNF) in retina and cortex, suggests that NGF might exert retino-fugal effects by affecting BDNF and its receptor TrkB. To address these questions, their expression and relationship with the GABAergic and glutamatergic transmission markers, GAD65 and GAD67, vesicular inhibitory amino acid transporter (VGAT), and vesicular glutamate transporters 1 and 2 (VGLUT-1 and VGLUT-2) were investigated in adult ONC rats contralateral and ipsilateral visual cortex (VCx). Ed-rhNGF recovers the ONC-induced alteration of GABAergic and glutamatergic markers in contralateral VCx, induces an upregulation of TrkB, which is positively correlated with BDNF precursor (proBDNF) decrease in both VCx sides, and strongly enhances TrkB+ cell soma and neuronal endings surrounded by GAD65 immuno-reactive afferents. These findings contribute to enlarging the knowledge on the mechanism of actions and cellular targets of exogenously administrated NGF, and suggest that ed-rhNGF might act by potentiating the activity-dependent TrkB expression in GAD+ cells in VCx following retina damage and/or ONC.

NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats

“…The main goal of the present study was to further investigate the role of VEGF/NGF interaction in the neuroretina by analyzing the effects of ed-NGF treatment in the STZ model of DR. As already showed by means of different models of retinal degenerations, ed-NGF are able to counteract RGC loss, and exerts protective and reparative actions through the normalization of neurotrophins and expression of TrkA receptors and its related intracellular pathways [ 21 , 23 , 33 , 34 ].…”

Brain‐derived neurotrophic factor in degenerative retinal diseases: Update and novel perspective

“…The advantage of eyes is that BDNF can be used locally to reduce its systemic side effects, but it needs to be given repeatedly, which will cause increasing risk of cataract, retinal ischemia, and endophthalmitis. (Rosso et al, 2021). These findings emphasized the role of NGF, especially BDNF, and provided a new perspective that eye administration might be a novel aspect in diseases involving both the brain and eyes, such as AD.…”

“…More interestingly, Rosso, Pamela et al suggested that, in the context of retina and optic nerve damage, NGF intravitreal injection strongly enhanced the activity‐dependent TrkB expression in contralateral and ipsilateral visual cortex to improve visual acuity (Rosso et al, 2021). These findings emphasized the role of NGF, especially BDNF, and provided a new perspective that eye administration might be a novel aspect in diseases involving both the brain and eyes, such as AD.…”

Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review)

“…A different study indicated that the exogenous application of NGF promoted glutamatergic synapse activity via binding to Trk receptors. This promotion of glutamatergic synapse activity was regulated by potentiating the pre-synaptic release of glutamate ( 89 ). These data suggested that NGF released by glioma cells may enhance the glutamatergic NGSs and promote glioma growth.…”