Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

Cillà, Stefano De; Farruggio, Serena; Vujosevic, Stela; Raina, Giulia; Filippini, Davide; Gatti, Valentina; Clemente, Nausicaa; Mary, David A.S.G.; Vezzola, Diego; Casini, Giovanni; Rossetti, Luca; Grossini, Elena

doi:10.1159/000479441

Cited by 3,606 publications

(50 citation statements)

References 130 publications

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“…Oxidative stress plays an important role in retinal angiogenesis [34,35]. HIF, the pivotal mediator of cellular responses to oxygen stress, was decreased by imatinib treatment [35]. This result suggests that imatinib might also suppress angiogenesis by ameliorating oxidative stress in retinas.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 95%

“…In addition, we found imatinib could inhibit the phosphorylation of Erk1/2, which is involved in the survival, proliferation, and migration of vascular cells and is recognized as part of an important signaling pathway closely involved in angiogenesis [33], suggesting that the reduction of angiogenesis by imatinib may occur in part through inhibiting Erk1/2 signaling pathways. Oxidative stress plays an important role in retinal angiogenesis [34,35]. HIF, the pivotal mediator of cellular responses to oxygen stress, was decreased by imatinib treatment [35].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

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Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-α and PDGFR-β

Zhou¹,

Sun²,

Huang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Platelet-derived growth factors (PDGFs) have emerged as pivotal in pathological angiogenesis, which is a hallmark of various tumors and retinal diseases. Here we evaluated the anti-angiogenic effect of imatinib, an inhibitor of PDGF receptors α and β (PDGFR-α and -β), in retinal neovascularization using an oxygen-induced retinopathy (OIR) model. Methods: The OIR model was established and given imatinib or vehicle treatments daily from P12 to P16. At the peak of angiogenesis at P17, the neovascularization area was quantified on retinal whole-mounts with isolectin B4 staining. Immunofluorescence staining and western blots were used to determine the effect of imatinib on different vascular cells and the pathway molecules involved. Results: Imatinib effectively suppressed pathological angiogenesis in OIR mice and reduced the number of all three types of vascular cells, including endothelial cells, pericytes, and smooth muscle cells. Moreover, the expression and activation of PDGFR-α and -β were inhibited by imatinib. The imatinib-treated OIR mice presented with reduced expression of other potent pro-angiogenic factors such as VEGF and FGF2. No obvious retinal or systemic side effects were observed in the imatinib treatment group. Conclusions: Imatinib appears to be safe and effective in suppressing retinal neovascularization. Targeting PDGFs/PDGFRs may also be important for anti-angiogenic treatment and offer a viable alternative treatment for retinal angiogenic diseases.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 95%

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-α and PDGFR-β

Zhou¹,

Sun²,

Huang³

et al. 2018

Cell Physiol Biochem

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“…GSH measurements were performed with a specific kit (Cayman Chemical), as previously performed (Grossini et al 2014;Surico et al 2015;De Cill a et al 2017).…”

Section: Gsh Assaymentioning

confidence: 99%

The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes

Cillà

Vezzola

Farruggio

et al. 2018

Acta Ophthalmologica

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Purpose Subthreshold micropulse laser (SMPL) has been increasingly used for the treatment of different retinal and choroidal macular disorders. However, the exact mechanisms of action have not yet been clearly defined. Therefore, we aimed to examine the role of SMPL treatment in the modulation of oxidant/antioxidant systems, apoptosis and autophagy in the mice eyes. Methods A specific laser contact lens for retina was positioned on the cornea of 40 mice (20 young and 20 old) in order to focus the laser on the eye fundus for SMPL treatment. Within 6 months, 20 animals received one treatment only, whereas the others were treated three times. Eye specimens underwent histological analysis and were used for thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) quantification, as well as for the superoxide dismutase 1 (SOD1) and the selenoprotein thioredoxin reductase 1 (TrxR1) expression evaluation. Western blot was performed for nitric oxide synthase (NOS) subtypes detection and to examine changes in apoptotic/autophagy proteins expression. Results SMPL treatment reduced TBARS and increased GSH and SOD1 in the mice eyes. It also reduced cytochrome c, caspase 3 expression and activity and cleaved caspase 9, and increased Beclin 1, p62 and LC3β. The effects were more relevant in the elderly animals. Conclusion Our results showed that SMPL therapy restored the oxidant/antioxidant balance within retinal layers and modulated programmed forms of cell death. Further studies may confirm these data and could evaluate their relevance in clinical practice.

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“…Since the expression of VEGF was intimately linked with the apoptosis state of RPE cells, which could be regulated by hyperoxidants, high glucose levels and cyclic stretch ( De Cillà et al, 2017 ; Oh et al, 2017 ; Wu et al, 2017 ), the beneficial effects of Kin against oxidative apoptosis were further analyzed. We found that Kin drastically reduced apoptosis of RPE cells compared with the H 2 O 2 -treated Vehicle group.…”

Section: Discussionmentioning

confidence: 99%

Kinsenoside Ameliorates Oxidative Stress-Induced RPE Cell Apoptosis and Inhibits Angiogenesis via Erk/p38/NF-κB/VEGF Signaling

Luo¹,

Gu²,

Zhang³

et al. 2018

Front. Pharmacol.

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The pathological superoxidative condition that retinal pigment epithelium (RPE) cells experience contributed to the advancement of age-related macular degeneration (AMD), which was accompanied by significant neovascularization. Therefore, the discovery of novel pharmacological candidates to ameliorate oxidative damage (H2O2) against RPE cells and inhibit the following angiogenesis simultaneously is urgently needed. Herein, we found that kinsenoside (Kin), an active component derived from Anoectochilus roxburghii, was able to protect RPE cells effectively and attenuate subsequent angiogenesis. In this study, H2O2-induced oxidative injury reduced RPE cell viability and increased cell apoptosis, which was significantly rescued by the treatment with Kin. Compared with H2O2 alone, Kin decreased the levels of Bax and increased the production of Bcl-2 in RPE cells. H2O2-stimulated VEGF up-regulation was inhibited by Kin treatment. Human umbilical vein endothelial cell (HUVEC) neovascularization induced by conditioned medium (CM) from H2O2-stimulated RPE cells was attenuated by treatment with Kin, VEGF antagonist, NF-κB, Erk-MAPK, and p38-MAPK inhibitors. Additionally, H2O2-activated phosphorylated expression of IκBα, p65, Erk, and p38 in RPE cells was inhibited by treatment with Kin. Taken together, Kin protected RPE from apoptosis against oxidative stress while simultaneously decreasing apoptosis-related neovascularization. This could be ascribed to the inhibition of Erk/p38/NF-κB signaling by Kin that contributed to the resulting decreased VEGF expression in H2O2-treated RPE cells.

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Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

Cited by 3,606 publications

References 130 publications

Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-α and PDGFR-β

Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-α and PDGFR-β

The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes

Kinsenoside Ameliorates Oxidative Stress-Induced RPE Cell Apoptosis and Inhibits Angiogenesis via Erk/p38/NF-κB/VEGF Signaling

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