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Int. J. Mol. Sci. 2017, 18(1), 98;

Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

San Raffaele Scientific Institute, Division of Neuroscience, Eye Repair Unit, 20132 Milan, Italy
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
National Research Council (CNR) Institute of Cell Biology & Neurobiology (IBCN), 00143 Rome, Italy
Department of Science, University Roma Tre, 00146 Rome, Italy
San Raffaele Scientific Institute, Division of Neuroscience, Institute of Experimental Neurology, 20132 Milan, Italy
Department of Sense Organs—Section of Ophthalmology, University of Rome “Sapienza”, 00185 Rome, Italy
Author to whom correspondence should be addressed.
Academic Editors: Margaret Fahnestock and Keri Martinowich
Received: 25 July 2016 / Revised: 20 December 2016 / Accepted: 24 December 2016 / Published: 5 January 2017
(This article belongs to the Special Issue Neurotrophic Factors—Historical Perspective and New Directions)
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Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration. View Full-Text
Keywords: optic-nerve crush; retinal ganglion cells; nerve growth factor; glaucoma optic-nerve crush; retinal ganglion cells; nerve growth factor; glaucoma

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Mesentier-Louro, L.A.; De Nicolò, S.; Rosso, P.; De Vitis, L.A.; Castoldi, V.; Leocani, L.; Mendez-Otero, R.; Santiago, M.F.; Tirassa, P.; Rama, P.; Lambiase, A. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells. Int. J. Mol. Sci. 2017, 18, 98.

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