Trans-Chalcone prevents VEGF expression and retinal neovascularization in the ischemic retina

Lamoke, Folami; Labazi, M.; Montemari, Anna Lisa; Parisi, G.; Varano, Monica; Bartoli, Manuela

doi:10.1016/j.exer.2011.02.007

Cited by 37 publications

(35 citation statements)

References 27 publications

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“…In the retina, oxidative stress induce by trauma, retinal neovascularization, and sterile inflammation may contribute to various eye diseases, including retinal ischemia and glaucoma [30]. As a CNS neuron, the optic nerve cannot regenerate after injury [1,2], except in certain special situations, such as in the case of oncomodulin stimulation [26], Mst3b-mediating axon regeneration [31], and intrinsic axon regeneration regulated by the Kruppel-like factor family [32].…”

Section: Discussionmentioning

confidence: 99%

Microglial TIR-domain-containing adapter-inducing interferon-β (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-κB

Liang

Zhang

et al. 2012

J Neuroinflammation

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BackgroundTIR-domain-containing adapter-inducing interferon-β (TRIF) is the sole downstream adaptor of Toll-like receptor (TLR)3, which is one of the major signaling pathways in immune cells leading to neuroinflammation in the central nervous system. Overexpression of TRIF may lead to activation of inflammatory responses, and contribute to pathophysiological progression in both acute and chronic neurodegenerative retinal diseases. In the present study, was aimed to elucidate the contributions of TRIF to optic nerve (ON) regeneration and retinal ganglion cell (RGC) survival following injury to the ON, a widely studied model of central nervous system injury and of degenerative diseases such as glaucoma.MethodsWe used retrograde labeling with a fluorochrome, hydroxystilbamidine (Fluorogold) to evaluate RGC survival, and immunostaining with growth-associated protein-43 to evaluate axon regeneration in an ON crush model. Changes in microglial cytokines following RGC injury was examined with ELISA and real-time PCR. In vivo studies were carried out in wild-type and trif-/- mice. A Transwell co-culture system and migration test were used to mimic the crosstalk between microglia and RGCs. TRIF-associated downstream adaptors were determined by western blotting.ResultsCompared with wild-type (WT) mice, TRIF knockout (KO) mice displayed a robust ability to regenerate axons 3 or 7 days after nerve injury. In addition, RGC survival was considerably higher in trif-/- than in WT mice. ON lesion induced less microglial activation in trif-/- than in WT mice. and more WT microglia distorted and migrated toward the foramen opticum. In the transwell system, few trif-/- microglia migrated through the membrane when stimulated by the performed lesion on RGC axons in a transwell system. Inactivation of microglial cells in trif-/- mice was associated with reduced production of inflammatory cytokines, as detected with real-time RT-PCR and ELISA. Furthermore western blot analysis showed that activation of known downstream effectors of TRIF, including TBK1, IKKε and NF-κB, were significantly inhibited by TRIF deficiency.ConclusionOur results indicate that TRIF deficiency promotes ON axon regeneration by attenuating microglial activation and consequently reducing the release of harmful cytokines via NF-κB inactivation.

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Section: Discussionmentioning

confidence: 99%

Microglial TIR-domain-containing adapter-inducing interferon-β (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-κB

Liang

Zhang

et al. 2012

J Neuroinflammation

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“…It is now apparent that VEGF plays a critical role both in retinal vascular development [52] and in pathologic angiogenesis in ischemic retinopathies and other forms of ocular neovascularization [53]. VEGF has been documented to be highly expressed in models of these processes [54]–[56].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-410 Reduces the Expression of Vascular Endothelial Growth Factor and Inhibits Oxygen-Induced Retinal Neovascularization

Chen

Wang

et al. 2014

PLoS ONE

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Retinal neovascularization (RNV) is an eye disease that can cause retinal detachment and even lead to blindness. RNV mainly occurs in the elderly population. The pathogenesis of RNV has been previously reported to be highly related to the expression of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF) and other angiogenic factors. It has also been reported that VEGFA and other factors associated with RNV could be regulated by certain microRNAs (miRNA), a group of small non-coding RNAs which are able to regulate the expression of many genes in vivo. Here, we demonstrate that the miRNA miR-410 is highly expressed in mice within two weeks after birth. miR-410 could suppress VEGFA expression through interaction with the 3′UTR of the VEGFA messenger RNA. Overexpressing a miR-410 mimic effectively suppresses VEGFA expression in various cell lines. Further experiments on oxygen-induced retinopathy (OIR) in mice revealed that eye drops containing large amounts of miR-410 efficiently downregulate VEGFA expression, prevent retinal angiogenesis and effectively treat RNV. These results not only show the underlying mechanism of how miR-410 targets VEGFA but also provide a potential treatment strategy for RNV that might be used in the near future.

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“…The concept of ICAM-1 inhibition has become a potential therapeutic strategy for the prevention of diabetic retinopathy (Joussen et al, 2001;Miyamoto et al, 1999). Some flavonoid compounds, such as hesperidin, trans-chalcone, and minocycline, were reported to possess properties to inhibit diabetic-induced (Lamoke et al, 2011) or ischemia-induced (Abcouwer et al, 2013;Shi et al, 2012) ICAM-1 expression in retina. Our immunofluorescence and Western blot analysis also clearly supported that silybin effectively inhibited the up-regulated ICAM-1 protein (Fig.…”

Section: Discussionmentioning

confidence: 99%

Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats

Zhang

Shi

Baskota

et al. 2014

European Journal of Pharmacology

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Trans-Chalcone prevents VEGF expression and retinal neovascularization in the ischemic retina

Cited by 37 publications

References 27 publications

Microglial TIR-domain-containing adapter-inducing interferon-β (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-κB

Microglial TIR-domain-containing adapter-inducing interferon-β (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-κB

MicroRNA-410 Reduces the Expression of Vascular Endothelial Growth Factor and Inhibits Oxygen-Induced Retinal Neovascularization

Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats

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