scholarly journals The Effects of Two Nrf2 Activators, Bardoxolone Methyl and Omaveloxolone, on Retinal Ganglion Cell Survival during Ischemic Optic Neuropathy

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1466
Author(s):  
Jia-Ying Chien ◽  
Yu-Yau Chou ◽  
Jhih-Wei Ciou ◽  
Fang-Yun Liu ◽  
Shun-Ping Huang
Keyword(s):  
Kidney Disease ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Optic Neuropathy ◽  
Visual Function ◽  
Anterior Ischemic Optic Neuropathy ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Antioxidative Stress ◽  
Anti Inflammatory

Nonarteritic anterior ischemic optic neuropathy (NAION) is one of the most common acute optic neuropathies that affect the over 55-year-old population. NAION causes the loss of visual function, and it has no safe and effective therapy. Bardoxolone methyl (methyl 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate; CDDO-Me; RTA 402) is a semisynthetic triterpenoid with effects against antioxidative stress and inflammation in neurodegeneration and kidney disease that activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Moreover, RTA 402 is an FDA-approved compound for the treatment of solid tumors, lymphoid malignancies, melanoma, and chronic kidney disease. Omaveloxolone (RTA 408) is an activator of Nrf2 and an inhibitor of NFκB, possessing antioxidative and anti-inflammatory activities in mitochondrial bioenergetics. RTA 408 is also under clinical investigation for Friedreich ataxia (FA). In this study, a rodent anterior ischemic optic neuropathy (rAION) model induced by photothrombosis was used to examine the therapeutic effects of RTA 402 and RTA 408. Treatment with RTA402 results in antiapoptotic, antioxidative stress, anti-inflammatory, and myelin-preserving effects on retinal ganglion cell (RGC) survival and visual function via regulation of NQO1 and HO-1, reduced IL-6 and Iba1 expression in macrophages, and promoted microglial expression of TGF-β and Ym1 + 2 in the retina and optic nerve. However, these effects were not observed after RTA 408 treatment. Our results provide explicit evidence that RTA 402 modulates the Nrf2 and NFκB signaling pathways to protect RGCs from apoptosis and maintain the visual function in an rAION model. These findings indicate that RTA 402 may a potential therapeutic agent for ischemic optic neuropathy.

scholarly journals Citicoline in ophthalmologic practice: neuroprotection in ischemic optic neuropathy, diabetic retinopathy and amblyopia

2021 ◽  
Vol 9 (1) ◽  
pp. 28-33
Author(s):  
L.P. Novak ◽  
O.V. Tumanova
Keyword(s):  
Diabetic Retinopathy ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Optic Neuropathy ◽  
Cell Function ◽  
Patient Adherence ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Endogenous Dopamine ◽  
Retinal Ganglion Cell Function

Decrease and loss of vision are extremely important problems, quite common conditions that lead to disability. The most common causes are ischemic optic neuropathy, diabetic retinopathy, and amblyopia. The pathogenesis of these disea­ses is characterized by neurodegeneration, loss of structure and function of neurons. Citicoline may be considered for neuroprotection as the drug of choice in these clinical situations. Citicoline has antioxidant and anti-inflammatory properties, it reduces lipid peroxidation and the formation of free radicals, has anti-apoptotic and membrane-protective effects. The drug has a neuromodulatory effect and also contributes to the pre­servation of sphingomyelin, which ensures signal transmission in nerve cells. In ischemic optic neuropathy, oral citicoline can reduce nerve fiber loss and improve retinal ganglion cell function and visual tract function. In diabetic retinopathy, citicoline prevents synapse loss and improves macular and retinal ganglion cell function. In amblyopia, citicoline stimulates the function of neurotransmitters and neuromodulators, including an increase in the activity of endogenous dopamine and, at the same time, an improvement in the vascular aspects of neurological function. Axobrex is a convenient oral form of citicoline. With oral administration, the bioavailability of citicoline exceeds 90 %, Axobrex is non-toxic and very well-tolerated. The dosage regimen of Axobrex is simple, which contributes to satisfactory patient adherence to treatment. The use of Axobrex in patients with ischemic optic neuropathy, diabetic retinopathy, and amblyopia has an optimal balance of benefits and safety and is advisable for neuroprotection.

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 Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Tian Wang ◽  
Yiming Li ◽  
Miao Guo ◽  
Xue Dong ◽  
Mengyu Liao ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Optic Neuropathy ◽  
Axon Regeneration ◽  
Retinal Ganglion ◽  
Traumatic Optic Neuropathy ◽  
Fiber Layer

Traumatic optic neuropathy (TON) refers to optic nerve damage caused by trauma, leading to partial or complete loss of vision. The primary treatment options, such as hormonal therapy and surgery, have limited efficacy. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), a functional endogenous neuroprotective peptide, has emerged as a promising therapeutic agent. In this study, we used rat retinal ganglion cell (RGC) exosomes as nanosized vesicles for the delivery of PACAP38 loaded via the exosomal anchor peptide CP05 (EXOPACAP38). EXOPACAP38 showed greater uptake efficiency in vitro and in vivo than PACAP38. The results showed that EXOPACAP38 significantly enhanced the RGC survival rate and retinal nerve fiber layer thickness in a rat TON model. Moreover, EXOPACAP38 significantly promoted axon regeneration and optic nerve function after injury. These findings indicate that EXOPACAP38 can be used as a treatment option and may have therapeutic implications for patients with TON.

scholarly journals Neuroprotective and Anti-Inflammatory Effects of a Hydrophilic Saffron Extract in a Model of Glaucoma

2019 ◽  
Vol 20 (17) ◽  
pp. 4110 ◽  
Author(s):  
Jose A. Fernández-Albarral ◽  
Ana I. Ramírez ◽  
Rosa de Hoz ◽  
Nerea López-Villarín ◽  
Elena Salobrar-García ◽  
...  
Keyword(s):  
Cell Death ◽  
Intraocular Pressure ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Retinal Ganglion Cell Death ◽  
Saffron Extract ◽  
Anti Inflammatory ◽  
Ganglion Cell Death

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs). An increase in the intraocular pressure is the principal risk factor for such loss, but controlling this pressure does not always prevent glaucomatous damage. Activation of immune cells resident in the retina (microglia) may contribute to RGC death. Thus, a substance with anti-inflammatory activity may protect against RGC degeneration. This study investigated the neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract standardized to 3% crocin content in a mouse model of unilateral, laser-induced ocular hypertension (OHT). Treatment with saffron extract decreased microglion numbers and morphological signs of their activation, including soma size and process retraction, both in OHT and in contralateral eyes. Saffron extract treatment also partially reversed OHT-induced down-regulation of P2RY12. In addition, the extract prevented retinal ganglion cell death in OHT eyes. Oral administration of saffron extract was able to decrease the neuroinflammation associated with increased intraocular pressure, preventing retinal ganglion cell death. Our findings indicate that saffron extract may exert a protective effect in glaucomatous pathology.

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