scholarly journals Algae Oil Treatment Protects Retinal Ganglion Cells (RGCs) via ERK Signaling Pathway in Experimental Optic Nerve Ischemia

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 83
Author(s):  
Tzu-Lun Huang ◽  
Yao-Tseng Wen ◽  
Yu-Chieh Ho ◽  
Jia-Kang Wang ◽  
Kuan-Hung Lin ◽  
...  

Background: We investigated the therapeutic effects and related mechanisms of algae oil (ALG) to protect retinal ganglion cells (RGCs) in a rat model of anterior ischemic optic neuropathy (rAION). Methods: Rats were daily gavaged with ALG after rAION induction for seven days. The therapeutic effects of ALG on rAION were evaluated using flash visual evoked potentials (FVEPs), retrograde labeling of RGCs, TUNEL assay of the retina, and ED1 staining of optic nerves (ONs). The levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, Cl-caspase-3, ciliary neurotrophic factor (CNTF), and p-ERK were analyzed by using western blots. Results: Protection of visual function in FVEPs amplitude was noted, with a better preservation of the P1–N2 amplitude in the ALG-treated group (p = 0.032) than in the rAION group. The density of RGCs was 2.4-fold higher in the ALG-treated group compared to that in the rAION group (p < 0.0001). The number of ED1-positive cells in ONs was significantly reduced 4.1-fold in the ALG-treated group compared to those in the rAION group (p = 0.029). The number of apoptotic RGCs was 3.2-fold lower in number in the ALG-treated group (p = 0.001) than that in the rAION group. The ALG treatment inhibited ERK activation to reduce the levels of iNOS, IL-1β, TNF-α, and Cl-caspase-3 and to increase the level of CNTF in the rAION model. Conclusion: The treatment with ALG after rAION induction inhibits ERK activation to provide both anti-inflammatory and antiapoptotic effects in rAION.

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 902
Author(s):  
Jia-Ying Chien ◽  
Shu-Fang Lin ◽  
Yu-Yau Chou ◽  
Chi-Ying F. Huang ◽  
Shun-Ping Huang

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute vision loss in older people, and there is no effective therapy. The effect of the systemic or local application of steroids for NAION patients remains controversial. Oroxylin A (OA) (5,7-dihydroxy-6-methoxyflavone) is a bioactive flavonoid extracted from Scutellariae baicalensis Georgi. with various beneficial effects, including anti-inflammatory and neuroprotective effects. A previous study showed that OA promotes retinal ganglion cell (RGC) survival after optic nerve (ON) crush injury. The purpose of this research was to further explore the potential actions of OA in ischemic injury in an experimental anterior ischemic optic neuropathy (rAION) rat model induced by photothrombosis. Our results show that OA efficiently attenuated ischemic injury in rats by reducing optic disc edema, the apoptotic death of retinal ganglion cells, and the infiltration of inflammatory cells. Moreover, OA significantly ameliorated the pathologic changes of demyelination, modulated microglial polarization, and preserved visual function after rAION induction. OA activated nuclear factor E2 related factor (Nrf2) signaling and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1 (HO-1) in the retina. We demonstrated that OA activates Nrf2 signaling, protecting retinal ganglion cells from ischemic injury, in the rAION model and could potentially be used as a therapeutic approach in ischemic optic neuropathy.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 647
Author(s):  
Henry T. Hsueh ◽  
Yoo-Chun Kim ◽  
Ian Pitha ◽  
Matthew D. Shin ◽  
Cynthia A. Berlinicke ◽  
...  

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.


BIOCELL ◽  
2008 ◽  
Vol 32 (2) ◽  
pp. 201-205 ◽  
Author(s):  
SAMIN HONG ◽  
KYOUNGSOO PARK ◽  
CHAN YUN KIM ◽  
GONG JE SEONG

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Shun Gong ◽  
Hai Jin ◽  
Danfeng Zhang ◽  
Wei Zou ◽  
Chunhui Wang ◽  
...  

Background. Existing evidence suggests the potential therapy of transplanting olfactory ensheathing cells (OEC) either alone or in combination with neurotrophic factors or other cell types in optic nerve injury (ONI). However, clinical use of autologous OEC in the acute stages of ONI is not possible. On the other hand, acute application of heterologous transplantation may bring the issue of immune rejection. The olfactory mucosa (OM) with OEC in the lamina propria layer is located in the upper region of the nasal cavity and is easy to dissect under nasal endoscopy, which makes it a candidate as autograft material in acute stages of ONI. To investigate the potential of the OM on the protection of injured neurons and on the promotion of axonal regeneration, we developed a transplantation of syngenic OM in rats with ONI model. Methods. After the right optic nerve was crushed in Lewis rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats undergoing phosphate buffered saline (PBS) injection were used as negative controls (NC). The authors evaluated the regeneration of retinal ganglion cells (RGCs) and axons for 3, 7, 14, and 28 days after transplantation. Obtained retinas and optic nerves were analyzed histologically. Results. Transplantations of OM significantly promoted the survival of retinal ganglion cells (RGCs) and axonal growth of RGCs compared with PBS alone. Moreover, OM group was associated with higher expression of GAP-43 in comparison with the PBS group. In addition to the potential effects on RGCs, transplantations of OM significantly decreased the expression of GFAP in the retinas, suggesting inhibiting astrocyte activation. Conclusions. Transplantation of whole-layer OM in rats contributes to the neuronal survival and axon regeneration after ONI.


2007 ◽  
Vol 28 (1) ◽  
pp. 137-155 ◽  
Author(s):  
Zelda H. Cheung ◽  
Mason C. P. Leung ◽  
Henry K. Yip ◽  
Wutian Wu ◽  
Flora K. W. Siu ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55291 ◽  
Author(s):  
Zhi-Yang Chang ◽  
Ming-Kung Yeh ◽  
Chiao-Hsi Chiang ◽  
Yi-Hao Chen ◽  
Da-Wen Lu

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Huimin Zhong ◽  
Huan Yu ◽  
Bo Chen ◽  
Lei Guo ◽  
Xing Xu ◽  
...  

Irreversible loss of retinal ganglion cells (RGCs) is a common pathological feature of various optic nerve degenerative diseases such as glaucoma and ischemic optic neuropathy. Effective protection of RGCs is the key to successful treatment of these diseases. Total Panax notoginseng saponins (TPNS) are the main active component of Panax notoginseng, which has an inhibitory effect on the apoptosis pathway. This study is aimed at assessing the protective effect of TPNS on RGCs of the optic nerve crush (ONC) model of rats and exploring the underlying mechanisms. The intraperitoneal or intravitreal injection of TPNS was used based on the establishment of the rat ONC model. Fifteen days after the injury, the cell membrane fluorescent probe (Fluoro-Gold) was applied to retrograde RGCs through the superior colliculus and obtain the number of surviving RGCs. TUNEL assay was also used to detect the number and density of RGC apoptosis after the ONC model. The expression and distribution of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK in the retina were demonstrated by Western blot analysis. After the intervention of TPNS, the rate of cell survival increased in different retinal regions ( p < 0.05 ) and the number of apoptosis cells decreased. Regarding the expression of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK-related apoptotic proteins, TPNS can reduce the level of apoptosis and play a role in protecting RGCs ( p < 0.05 ). These findings indicate that topical administration of TPNS can inhibit cell apoptosis and promote RGC survival in the crushed optic nerve.


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