JNK/c-Jun-driven NLRP3 inflammasome activation in microglia contributed to retinal ganglion cells degeneration induced by indirect traumatic optic neuropathy

2021 ◽  
Vol 202 ◽  
pp. 108335
Author(s):  
Xiaoqi Chu ◽  
Chun Wang ◽  
Zheng Wu ◽  
Liting Fan ◽  
Chunmei Tao ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Neuropathy ◽  
Nlrp3 Inflammasome ◽  
Ganglion Cells ◽  
Inflammasome Activation ◽  
Retinal Ganglion ◽  
Traumatic Optic Neuropathy ◽  
Nlrp3 Inflammasome Activation

Treatment of traumatic optic neuropathy using human placenta-derived mesenchymal stem cells in Asian patients

2020 ◽  
Vol 15 (10) ◽  
pp. 2163-2179
Author(s):  
Youngje Sung ◽  
Sang Min Lee ◽  
Mira Park ◽  
Hye Jeong Choi ◽  
Sukho Kang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Traumatic Optic Neuropathy ◽  
Asian Patients

Aim: To assess the safety and feasibility of subtenon transplantation of human placenta-derived mesenchymal stem cells (hPMSCs) in Asian patients with traumatic optic neuropathy. Materials & methods: The survival of retinal ganglion cells in the rat retina was evaluated by monitoring the expression of Tuj1 and Gfap after optic nerve compression. Based on the preclinical data, we conducted a Phase I, open label, single center, nonrandomized clinical trial in four Asian traumatic optic neuropathy patients. The safety and ophthalmologic changes were evaluated. Results: The levels of Tuj1 and Gfap expression were significantly increased in the hPMSC treatment group compared with the sham group, suggesting a protective effect of hPMSCs on the optic nerve and retinal ganglion cells. There was no evidence of adverse proliferation, tumorigenicity, severe inflammation or other serious issues during the 12-month follow-up period. Visual acuity improved in all four patients. Conclusion: The results suggested that hPMSCs are safe and have potential utility in regenerative medicine. Clinical trial registration number: 20150196587 (Korean FDA), 2015-07-123-054 (IRB).

scholarly journals Protective Effects of Oroxylin A on Retinal Ganglion Cells in Experimental Model of Anterior Ischemic Optic Neuropathy

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
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Ischemic Injury ◽  
Anterior Ischemic Optic Neuropathy ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Oroxylin A

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.

scholarly journals Targeting the NLRP3 Inflammasome in Glaucoma

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1239
Author(s):  
Sophie Coyle ◽  
Mohammed Naeem Khan ◽  
Melody Chemaly ◽  
Breedge Callaghan ◽  
Chelsey Doyle ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Cytokine ◽  
Therapeutic Strategy ◽  
Ganglion Cells ◽  
Axon Degeneration ◽  
Retinal Ganglion ◽  
Hypothetical Mechanism ◽  
Key Driver ◽  
Neuroprotective Therapies

Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30–40% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented.

The Photopic Negative Response evaluation in patients with Leber's hereditary optic neuropathy

2021 ◽  
pp. 216-219
Author(s):  
M.S. Shmelkova ◽  
◽  
N.L. Sheremet ◽  
I.A. Ronzina ◽  
N.A. Andreeva ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Ganglion Cells ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Negative Response ◽  
Photopic Negative Response ◽  
Control Group ◽  
Retinal Ganglion ◽  
Leber's Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy

Purpose. To assess the retinal ganglion cells function in patients with Leber's hereditary optic neuropathy (LHON) by registering the photopic negative response (PhNR) while the photopic electroretinography is performed. Material and methods. 14 patients with different LHON mutations and 9 healthy individuals were examined. A standard ophtalmological examination was performed, including visual fields, spectral optical coherence tomography, photopic electroretinography and PhNR tests. Results. Significant differences in the PhNR latency (68.4±4.01/64.28±5.37, p<0,01) and the PhNR amplitude (21.5±9.34/32.72±12.73, p<0,003) were revealed in patients with LHON and the control group. The study revealed significant differences between the PhNR latency (р<0.01) and the PhNR amplitude (р<0.008) in patients with visual acuity (VA) ≤ 0.1 and the control group, and between the PhNR amplitude in patients with VA≥0.13 and the control group (р<0.05). There were found significant correlations between the PhNR parameters and visual acuity, mean sensitivity, RNFL and GCC thickness. A strong positive correlation was found between the PhNR amplitude and the GCC thickness in patients with VA≥0.3. Conclusion. The PhNR parameters reflect the retinal ganglion cells function in patients with LHON and correlate with RNFL and GCC structural changes. Key words: Leber hereditary optic neuropathy, mitochondrial optical neuropathies, retinal ganglion cell, photopic negative response, PhNR.

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