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VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis.

ABSTRACT: Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ)-induced diabetes in rats and Macugen intravitreal injection in mice leads to retinal apoptosis in retinal ganglion cell and outer nuclear layers respectively. Importantly, VEGF-B treatment by intravitreal injection markedly reduced retinal apoptosis in both models. We further reveal that VEGF-B and its receptors, vascular endothelial growth factor 1 (VEGFR1) and neuropilin 1 (NP1), are abundantly expressed in rat retinae and choroids and are upregulated by high glucose with concomitant activation of Akt and Erk. These data highlight an important function of VEGF-B in protecting retinal cells from apoptosis induced by hyperglycemia and VEGF-A inhibition. VEGF-B may therefore have a therapeutic potential in treating various retinal degenerative diseases, and modulation of VEGF-B activity in the eye needs careful consideration.

SUBMITTER: Huang D

PROVIDER: S-EPMC4870690 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis.

Huang Delong D Zhao Chen C Ju Rong R Kumar Anil A Tian Geng G Huang Lijuan L Zheng Lei L Li Xianglin X Liu Lixian L Wang Shasha S Ren Xiangrong X Ye Zhimin Z Chen Wei W Xing Liying L Chen Qishan Q Gao Zhiqin Z Mi Jia J Tang Zhongshu Z Wang Bin B Zhang Shuping S Lee Chunsik C Li Xuri X

Scientific reports 20160518

Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ)-induced diabetes in rats and Mac ...[more]

PMID: 27189805

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Project description:The present study aimed to investigate the significant role of ?-elemene in mouse models of oxygen-induced retinopathy (OIR). C57BL/6J neonatal mice were used to establish OIR models. They were divided into four groups: Normoxia, OIR, OIR control and OIR?treated. Mice in the OIR group were exposed to 75±5% oxygen for 5 days and returned to a normal oxygen environment on postnatal day 12 (P12). The OIR treated group was intravitreally injected with 1 µl ??elemene on P12 and subsequently returned to a normal oxygen environment for 5 days (P12?P17). Retinas were obtained on P17. Retinal neovascularization (RNV) was detected using adenosine diphosphatase staining and analyzed by counting the nuclei of neovascular endothelial cells. Vascular endothelial growth factor (VEGF) expression was determined by reverse transcription?quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. MicroRNA (miRNA/miR) microarrays were used to screen out differentially expressed miRNAs between the OIR and ??elemene?treated groups. Binding the 3'?untranslated region (UTR) of VEGF and miR?27a was confirmed using luciferase assays. It was found that high oxygen concentrations accelerated RNV and increased the number of preretinal neovascular cells; ??elemene treatment reduced these effects. VEGF mRNA and protein expression was higher in the OIR and OIR control groups, compared with the normoxia and OIR?treated groups. Further, it was shown that miR?22, miR?181a?1, miR?335?5p, miR?669n, miR?190b, miR?27a and miR?93 were upregulated in the OIR?treated group, and downregulated in the OIR group. The prediction websites TargetScan and miRanda revealed that VEGF contained a potential miR?27a binding site in its 3'?untranslated region (UTR). Luciferase assays demonstrated that miR?27a directly bound to the 3'?UTR of VEGF. In vitro experiments demonstrated that miR?27a inhibited VEGF expression. In addition, ??elemene treatment upregulate miR?27a expression in vivo and in vitro. When miR?27a expression was depleted by miR?27a inhibitor, the protective effect of ??elemene on RNV was eliminated. The present study demonstrated that ??elemene reduced RNV in mouse OIR models via miR?27a upregulation, leading to reduced VEGF expression. This finding may contribute to the development of novel therapeutic strategies for human retinopathy.

Dataset Information

VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis.

Publications

VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis.

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