Inhibition of caspase-3-like activity reduces glutamate induced cell death in adult rat retina11Published on the World Wide Web on 9 May 2001.

Chen, T.A; Yang, Fusheng; Cole, Greg M.; Chan, Sun On

doi:10.1016/s0006-8993(01)02485-4

Cited by 56 publications

(57 citation statements)

References 52 publications

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“…We showed recently that phosphorylation of JNK is pro-apoptotic in NMDA-induced cell death in the RGCL (Munemasa et al, 2005). We note that caspase-3 activation may contribute to glutamateinduce apoptosis in the retina (Chen et al, 2001), and it is of interest that SP600125, a JNK inhibitor, suppresses activation of caspase-3 and subsequent apoptosis in midbrain dopaminergic neurons (Peng et al, 2004). These findings suggest that caspase-3 acts downstream of the JNK/c-Jun pathway, and suppression of caspase-3 activation may therefore be associated with the protective mechanism of c-Jun AS ODN.…”

Section: Effect Of C-jun As Odn On Nmda-induced Neurotoxicitymentioning

confidence: 65%

Pro‐apoptotic role of c‐Jun in NMDA‐induced neurotoxicity in the rat retina

Munemasa¹,

Ohtani-Kaneko²,

Kitaoka³

et al. 2006

J of Neuroscience Research

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We examined the role of c-Jun on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. An increase in c-Jun mRNA, c-Jun protein and phosphorylated c-Jun (p-c-Jun) levels in the retina was detected 3 hr after intravitreal injection of NMDA (20 nmol). These levels peaked after 12 hr, and then returned to their control levels by 24 hr. c-Jun and p-c-Jun immunoreactivities were observed in the retinal ganglion cell layer (RGCL), especially in retinal ganglion cells (RGCs), and in the inner nuclear layer (INL) 12 hr after NMDA injection, and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive cells were immunopositive for c-Jun and p-c-Jun. A c-Jun antisense oligodeoxynucleotide (AS ODN), which was simultaneously injected with NMDA, penetrated the cells in the RGCL and the INL, suppressed the NMDA-induced increase in c-Jun and p-c-Jun protein levels and reduced the number of TUNEL-positive cells in the RGCL 12 hr after the injection. The protective effect of c-Jun AS ODN on the NMDA-treated retina was also shown by the RGCL cell count and measurement of the IPL thickness, as well as by quantitative real-time PCR analysis of Thy-1 mRNA 7 days after the injection. These results suggest that c-Jun synthesis and phosphorylation participate in NMDA-induced neuronal cell death.

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Section: Effect Of C-jun As Odn On Nmda-induced Neurotoxicitymentioning

confidence: 65%

Pro‐apoptotic role of c‐Jun in NMDA‐induced neurotoxicity in the rat retina

Munemasa¹,

Ohtani-Kaneko²,

Kitaoka³

et al. 2006

J of Neuroscience Research

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“…Since the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is the major transmitter released from amacrine cells, impairment of amacrine cells by rotenone may reduce the inhibitory input from GABA on the ganglion cells. The resulting metabolic overactivation of ganglion cells, as indicated by cytochrome oxidase activity in the IPL and optic nerve, may lead to excitotoxic death of ganglion cells through apoptosis (Choi, 1995;Chen et al, 2001;Mattson, 2003). Excitotoxicity, triggered by excessive activation of glutamate receptors, has been postulated as a mechanism of neuronal death in a number of neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases (Choi, 1988;Coyle and Puttfarcken, 1993), as well as some eye diseases such as glaucoma and ischemic/ hypoxic attack (Dreyer et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Methylene blue prevents neurodegeneration caused by rotenone in the retina

2006

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An experimental optic neuropathy model was used to test the hypothesis that methylene blue may protect the retinal ganglion cell layer from neurodegeneration caused by rotenone. Rotenone is a widely used pesticide that inhibits complex I, the first enzyme of the mitochondrial respiratory chain. Complex I dysfunction is linked to the degeneration of retinal ganglion cells in Leber's optic neuropathy. Methylene blue is a reduction-oxidation agent that can act as a powerful antioxidant and also as an enhancer of the electron transport chain, preventing formation of mitochondrial oxygen free radicals and promoting oxygen consumption. The neurodegeneration of the retina was studied in mice with intravitreal microinjection of rotenone alone, or in combination with increasing doses of methylene blue, in one eye, and the vehicle in the contralateral control eye. The effect of rotenone and rotenone plus methylene blue was investigated using two histological stains, complex I and Nissl, and two measurements, morphometric layer thickness and non-biased stereological cell counts. Rotenone induced neurodegeneration in the retinal ganglion cell layer 24 h after injection, as indicated by significant reductions in both the thickness and cell numbers of the retinal ganglion cell layer of eyes microinjected with rotenone as compared to the control eyes. This neurodegeneration was prevented in a dose dependent manner by the injection of methylene blue along with rotenone. It was concluded that rotenone-induced degeneration in the ganglion cell layer can be prevented by intravitreal injection of methylene blue. In vitro experiments showed that methylene blue is both a powerful antioxidant as well as an enhancer of cellular oxygen consumption and is able to reverse the oxidative stress and decrease in oxygen consumption induced by rotenone in brain homogenates. The findings suggest that methylene blue may be a promising neuroprotective agent in optic neuropathy and perhaps other neurodegenerative diseases caused by mitochondrial dysfunction.

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“…21 Immunofluoresence analysis and western blots revealed that hyperglycemia increased the level of cleaved caspase-3, whereas MIAT knockdown partially decreased caspase-3 upregulation ( Figure 2D and 2E). Akt is a serine/ threonine kinase regulated by the membrane levels of phosphatidylinositol 3-phosphate.…”

Section: Systemic Effect Of Miat Knockdown On Visual Functionmentioning

confidence: 94%

lncRNA-MIAT Regulates Microvascular Dysfunction by Functioning as a Competing Endogenous RNA

Yan

Yao

Liu

et al. 2015

Circulation Research

554

474

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Rationale: Pathological angiogenesis is a critical component of diseases, such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, such as cell proliferation, cell motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes mellitus–induced microvascular dysfunction is largely unknown. Objective: To elucidate whether lncRNA-myocardial infarction–associated transcript (MIAT) is involved in diabetes mellitus–induced microvascular dysfunction. Methods and Results: Using quantitative polymerase chain reaction, we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and endothelial cells cultured in high glucose medium. Visual electrophysiology examination, TUNEL staining, retinal trypsin digestion, vascular permeability assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated diabetes mellitus–induced retinal microvascular dysfunction in vivo, and inhibited endothelial cell proliferation, migration, and tube formation in vitro. Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro studies revealed that MIAT functioned as a competing endogenous RNA, and formed a feedback loop with vascular endothelial growth factor and miR-150-5p to regulate endothelial cell function. Conclusions: This study highlights the involvement of lncRNA-MIAT in pathological angiogenesis and facilitates the development of lncRNA-directed diagnostics and therapeutics against neovascular diseases.

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Inhibition of caspase-3-like activity reduces glutamate induced cell death in adult rat retina11Published on the World Wide Web on 9 May 2001.

Cited by 56 publications

References 52 publications

Pro‐apoptotic role of c‐Jun in NMDA‐induced neurotoxicity in the rat retina

Pro‐apoptotic role of c‐Jun in NMDA‐induced neurotoxicity in the rat retina

Methylene blue prevents neurodegeneration caused by rotenone in the retina

lncRNA-MIAT Regulates Microvascular Dysfunction by Functioning as a Competing Endogenous RNA

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