scholarly journals 7,8-Dihydroxiflavone Protects Adult Rat Axotomized Retinal Ganglion Cells through MAPK/ERK and PI3K/AKT Activation

2021 ◽  
Vol 22 (19) ◽  
pp. 10896
Author(s):  
Caridad Galindo-Romero ◽  
Beatriz Vidal-Villegas ◽  
Javier Asís-Martínez ◽  
Fernando Lucas-Ruiz ◽  
Alejandro Gallego-Ortega ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Mitogen Activated Protein Kinase ◽  
Retinal Ganglion ◽  
Sprague Dawley ◽  
Akt Activation ◽  
Adult Rat ◽  
Phosphorylated Akt ◽  
Mitogen Activated Protein ◽  
Signaling Activation

We analyze the 7,8-dihydroxyflavone (DHF)/TrkB signaling activation of two main intracellular pathways, mitogen-activated protein kinase (MAPK)/ERK and phosphatidylinositol 3 kinase (PI3K)/AKT, in the neuroprotection of axotomized retinal ganglion cells (RGCs). Methods: Adult albino Sprague-Dawley rats received left intraorbital optic nerve transection (IONT) and were divided in two groups. One group received daily intraperitoneal DHF (5 mg/kg) and another vehicle (1%DMSO in 0.9%NaCl) from one day before IONT until processing. Additional intact rats were employed as control (n = 4). At 1, 3 or 7 days (d) after IONT, phosphorylated (p)AKT, p-MAPK, and non-phosphorylated AKT and MAPK expression levels were analyzed in the retina by Western blotting (n = 4/group). Radial sections were also immunodetected for the above-mentioned proteins, and for Brn3a and vimentin to identify RGCs and Müller cells (MCs), respectively (n = 3/group). Results: IONT induced increased levels of p-MAPK and MAPK at 3d in DHF- or vehicle-treated retinas and at 7d in DHF-treated retinas. IONT induced a fast decrease in AKT in retinas treated with DHF or vehicle, with higher levels of phosphorylation in DHF-treated retinas at 7d. In intact retinas and vehicle-treated groups, no p-MAPK or MAPK expression in RGCs was observed. In DHF- treated retinas p-MAPK and MAPK were expressed in the ganglion cell layer and in the RGC nuclei 3 and 7d after IONT. AKT was observed in intact and axotomized RGCs, but the signal intensity of p-AKT was stronger in DHF-treated retinas. Finally, MCs expressed higher quantities of both MAPK and AKT at 3d in both DHF- and vehicle-treated retinas, and at 7d the phosphorylation of p-MAPK was higher in DHF-treated groups. Conclusions: Phosphorylation and increased levels of AKT and MAPK through MCs and RGCs in retinas after DHF-treatment may be responsible for the increased and long-lasting RGC protection afforded by DHF after IONT.

scholarly journals Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing

2013 ◽  
Vol 6 (1) ◽  
pp. 015001 ◽  
Author(s):  
Barbara Lorber ◽  
Wen-Kai Hsiao ◽  
Ian M Hutchings ◽  
Keith R Martin
Keyword(s):  
Retinal Ganglion Cells ◽  
Inkjet Printing ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Adult Rat

scholarly journals Ih Without Kir in Adult Rat Retinal Ganglion Cells

2007 ◽  
Vol 97 (5) ◽  
pp. 3790-3799 ◽  
Author(s):  
Sherwin C. Lee ◽  
Andrew T. Ishida
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Reversal Potential ◽  
Inward Rectification ◽  
Retinal Ganglion ◽  
Membrane Hyperpolarization ◽  
Adult Rat ◽  
Inwardly Rectifying ◽  
Cell Somata

Antisera directed against hyperpolarization-activated mixed-cation (“ Ih”) and K+ (“Kir”) channels bind to some somata in the ganglion cell layer of rat and rabbit retina. Additionally, the termination of hyperpolarizing current injections can trigger spikes in some cat retinal ganglion cells, suggesting a rebound depolarization arising from activation of Ih. However, patch-clamp studies showed that rat ganglion cells lack inward rectification or present an inwardly rectifying K+ current. We therefore tested whether hyperpolarization activates Ih in dissociated, adult rat retinal ganglion cell somata. We report here that, although we found no inward rectification in some cells, and a Kir-like current in a few cells, hyperpolarization activated Ih in roughly 75% of the cells we recorded from in voltage clamp. We show that this current is blocked by Cs+ or ZD7288 and only slightly reduced by Ba2+, that the current amplitude and reversal potential are sensitive to extracellular Na+ and K+, and that we found no evidence of Kir in cells presenting Ih. In current clamp, injecting hyperpolarizing current induced a slowly relaxing membrane hyperpolarization that rebounded to a few action potentials when the hyperpolarizing current was stopped; both the membrane potential relaxation and rebound spikes were blocked by ZD7288. These results provide the first measurement of Ih in mammalian retinal ganglion cells and indicate that the ion channels of rat retinal ganglion cells may vary in ways not expected from previous voltage and current recordings.

Expression of CB2 cannabinoid receptor mRNA in adult rat retina

2000 ◽  
Vol 17 (1) ◽  
pp. 91-95 ◽  
Author(s):  
QINGJUN LU ◽  
ALEX STRAIKER ◽  
QINGXIAN LU ◽  
GREG MAGUIRE
Keyword(s):  
Retinal Ganglion Cells ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Ganglion Cells ◽  
Mouse Tissue ◽  
Retinal Ganglion ◽  
Rt Pcr ◽  
Rat Retina ◽  
Adult Rat ◽  
Receptor Mrna

To date, two cannabinoid receptors, CB1 and CB2, have been cloned. The CB1 receptor has been found in a variety of tissues, particularly in the brain. CB2 receptor mRNA is mainly expressed in the immune system, though one group has found it in mouse cerebellum. Previous immunostaining studies in our lab demonstrated the presence of CB1 receptors in the retina though little evidence exists for the presence of CB2. The putative endogenous ligand for CB2 has been found in retina, however, suggesting that further study of CB2 in retina is warranted. Because glutamate is toxic to retinal ganglion cells in glaucoma and activation of CB2 receptors may be able to protect neurons from glutamate-induced death, we examined the expression of CB2 mRNA in adult rat retina in order to better understand possible neuroprotective mechanisms relevant to glaucoma. Using in situ hybridization, we demonstrated that CB2 cannabinoid receptor messenger RNA was clearly expressed in the adult rat retina, including the somas of retinal ganglion cells. Antisense cRNA probe detected strong signals in the retinal ganglion cell layer, the inner nuclear layer, and the inner segments of photoreceptor cells. Using reverse transcription polymerase chain reaction (RT-PCR) in both rat and mouse tissue, we obtained an RT-PCR product with the same sequence as that reported for CB2 in the GenBank database, thus confirming the presence of CB2 mRNA in retina. The presence of CB2 in retina provides new evidence for the presence of CB2 in the central nervous system (CNS) and an excellent model for its study.

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