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

Abstract

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.

• Authors: Louise A Mesentier-Louro, Sara De Nicolò, Pamela Rosso, Luigi A De Vitis, Valerio Castoldi, Letizia Leocani, Rosalia Mendez-Otero, Marcelo F Santiago, Paola Tirassa, Paolo Rama, Alessandro Lambiase
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 1 (Jan 05 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 28067793 (Publication Type: Journal Article)

Chemical References

• GFAP protein, rat
• Glial Fibrillary Acidic Protein
• Nerve Growth Factors
• Nerve Tissue Proteins
• Protein Precursors
• Receptors, Nerve Growth Factor
• pro-nerve growth factor, rat
• Nerve Growth Factor
• Receptor, trkA

Topics

• Animals
• Apoptosis
• Blotting, Western
• Evoked Potentials, Visual (physiology)
• Glial Fibrillary Acidic Protein (metabolism)
• Male
• Microscopy, Fluorescence
• Nerve Crush
• Nerve Growth Factor (metabolism)
• Nerve Growth Factors (metabolism)
• Nerve Tissue Proteins (metabolism)
• Optic Nerve Injuries (complications)
• Protein Precursors (metabolism)
• Rats
• Rats, Long-Evans
• Receptor, trkA (metabolism)
• Receptors, Nerve Growth Factor (metabolism)
• Retina (metabolism, physiopathology)
• Retinal Degeneration (etiology, metabolism, physiopathology)
• Retinal Ganglion Cells (metabolism)
• Signal Transduction
• Time Factors