Hyperglycemia promotes vasculogenesis in choroidal neovascularization in diabetic mice by stimulating VEGF and SDF-1 expression in retinal pigment epithelial cells

Cai, Yan; Li, Xia; Wang, Yusheng; Shi, Yuanyuan; Ye, Zi; Yang, Guodong; Dou, Guo‐Rui; Hou, Huiyuan; Yang, Nan; Cao, Xiaohong; Lu, Zifan

doi:10.1016/j.exer.2014.04.012

Cited by 25 publications

(9 citation statements)

References 44 publications

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“…Furthermore, we determined the influence of MT-1/2 on CNV by using the laser-induced CNV model. Previously, MT-1/2 was shown to be involved in pancreas function 35 and high glucose levels to promote angiogenesis 36 ; however, the blood glucose level in MT-1/2 KO mice was not significantly changed compared with that in WT mice (WT mice: 170. 7 CNV lesions in the eyes of MT-1/2 KO mice was significantly smaller than that observed in WT mice (Figs.…”

Section: The Role Of Mt-1/2 In Ocular Neovascularizationmentioning

confidence: 99%

Role of Metallothioneins 1 and 2 in Ocular Neovascularization

Nakamura

Shimazawa

Inoue

et al. 2014

Investigative Ophthalmology & Visual Science

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Section: The Role Of Mt-1/2 In Ocular Neovascularizationmentioning

confidence: 99%

Role of Metallothioneins 1 and 2 in Ocular Neovascularization

Nakamura

Shimazawa

Inoue

et al. 2014

Investigative Ophthalmology & Visual Science

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“…VEGF is produced by differentiated human RPE cells in vitro and in vivo and also involved in paracrine signaling between the RPE and the CC [40]. Hyperglycemia has been reported to induce the level of VEGF in the retina [41], RPE [42] and retinal endothelial cells [43]. Also, an increased level of VEGF mRNA in retina has been detected in DR and ROP [44].…”

Section: Discussionmentioning

confidence: 99%

Prorenin receptor (PRR)-mediated NADPH oxidase (Nox) signaling regulates VEGF synthesis under hyperglycemic condition in ARPE-19 cells

Haque

Iuvone

et al. 2017

Journal of Receptors and Signal Transduction

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The stimulation of angiotensin II (Ang II), the effector peptide of renin–angiotensin system, has been reported to increase the expression of vascular endothelial growth factor (VEGF) through the activation of the Ang II type 1 receptor (AT1R). In this study, we investigated whether hyperglycemia (HG, 33 mM glucose) in ARPE-19 cells could promote the expression of VEGF independently of Ang II through prorenin receptor (PRR), via an NADPH oxidase (Nox)-dependent mechanism. ARPE-19 cells were treated with the angiotensin converting enzyme (ACE) inhibitor perindopril to block the synthesis of Ang II. Treatment with HG induced VEGF expression in ARPE-19 cells, which was attenuated by pretreatment with the inhibitors of Nox, but not those of nitric oxide synthase, xanthine oxidase and mitochondrial O2 synthesis. In addition, Nox-derived O2− and H2O2 signaling in the regulation of VEGF was determined by using both polyethylene glycol (PEG)-catalase (CAT) and PEG-superoxide dismutase (SOD). We demonstrated that small interfering RNA (siRNA)-mediated knockdown of PRR, Nox2 and Nox4 significantly reduced the HG-induced stimulation of VEGF. On the other hand, Nox4 overexpression significantly potentiated PRR-induced stimulation of VEGF under hyperglycemia in ARPE-19 cells. Furthermore, Nox4 was shown to be associated with enhanced activities of ERK1/2 and NF-κB (p65), indicating their involvement in PRR-induced activation of VEGF under HG in ARPE-19 cells. Our results support the hypothesis that Nox4-derived reactive oxygen species (ROS) signaling is implicated in the hyperglycemia-induced increase of VEGF expression through PRR in ARPE-19 cells. However, further work is needed to evaluate the role of PRR and Nox-s in HG-induced stimulation of VEGF in vivo.

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“…FFA images were captured 2-5 min after intraperitoneal injection of 0.3 ml 2% fluorescein sodium (Guangxi Yinzhou People's Pharmaceutical Co., Ltd.) (29). Angiograms were graded as follows: Not stained, score 0; slightly stained, score 1; moderately stained, score 2; strongly stained, score 3 (30,31).…”

Section: Fundus Fluorescein Angiography (Ffa)mentioning

confidence: 99%

Pirfenidone ameliorates the formation of choroidal neovascularization in mice

Bao

Huang

et al. 2020

Mol Med Report

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The formation and development of choroidal neovascularization (cnV) is accompanied by inflammation and fibrosis. Existing treatments are expensive and can cause irreversible complications. Pirfenidone (PFD) exerts anti-inflammatory and anti-fibrotic effects; however, its applications in the eye remain unclear. Male C57BL/6J mice (aged 6-8 weeks) were used to explore whether PFD can inhibit the formation of laser-induced CNV. The localization of transforming growth factor β 2 (TGFβ 2 ) was determined through immunofluorescent staining. After laser photocoagulation, the vehicle and PFD groups were intravitreally injected with 1 µl PBS and 1 µl 0.5% PFD, respectively. At day 7 after intravitreal injection, the expression of TGFβ 2 and vascular endothelial growth factor (VEGF) was assessed. Fundus fluorescein angiography was performed to investigate the extent of fluorescence leakage, and the CNV areas were analyzed using a choroidal flat mount. The results demonstrated that, on day 7 after photocoagulation, the expression of TGFβ 2 and VEGF was reduced in the experimental group. In addition, fluorescein angiography showed that the leakage area of CNV was significantly smaller in the PFD injection group than those observed in the control and vehicle groups. Moreover, the areas of CNV in the PFD injection group were smaller compared with those reported in the other two injection groups. Histopathological and Tunel analyses performed on day 28 revealed that there were no notable abnormalities on the layers of the neural retina of PFD-treated mice. In conclusion, intravitreal injection of PFD inhibited the formation of CNV in mice, likely via the downregulation of VEGF and TGFβ 2 , which did not cause damage to the mouse retina after 28 days of treatment.

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Hyperglycemia promotes vasculogenesis in choroidal neovascularization in diabetic mice by stimulating VEGF and SDF-1 expression in retinal pigment epithelial cells

Cited by 25 publications

References 44 publications

Role of Metallothioneins 1 and 2 in Ocular Neovascularization

Role of Metallothioneins 1 and 2 in Ocular Neovascularization

Prorenin receptor (PRR)-mediated NADPH oxidase (Nox) signaling regulates VEGF synthesis under hyperglycemic condition in ARPE-19 cells

Pirfenidone ameliorates the formation of choroidal neovascularization in mice

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