title: Potential suppression of the high glucose and insulin-induced retinal neovascularization by Sirtuin 3 in the human retinal endothelial cells.
abstract: Retinal neovascularization generally play roles in the formation of various severe eye diseases, such as age-related macular degeneration and diabetic retinopathy. The regulation of neovascularization-related pathways by Sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, give us a cue that Sirt3 may participate in the retinal neovascularization. However, the mechanism remains unclear. Here, we established a retinal neovascularization model by using human retinal endothelial cells (HRECs) under the induction of high glucose and insulin (HGI). With this model, Sirt3-expressing lentivirus was constructed and then used to investigate the effect of Sirt3 overexpression on the expression of migration-, neovascularization- and autophagy-related genes. After the treatment of HGI on HRECs, the mRNA and protein levels of migration-related genes, including matrix metalloproteinase-2 (MMP-2) and MMP-9, were significantly upregulated. Meanwhile, angiogenesis-related genes, including vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α), and insulin-like growth factor-1 (IGF-1) were promoted at both mRNA and protein levels. However, HGI had no clear effect on the mRNA and protein levels of microtubule associated protein 1 light chain 3 (LC3), an autophagy-related gene. When Sirt3 was overexpressed by lentivirus infection after HGI, the upregulation of MMP-2, MMP-9, VEGF, HIF-1α, and IGF-1 were suppressed at both transcription and translation levels. At the same time, LC3 mRNA and LC3-II protein increased. These results suggest that Sirt3 may inhibit retinal neovascularization by regulating the migration-, neovascularization- and autophagy-related factors expression. Thus we argue that Sirt3 may be a potential candidate drug for curing various eye diseases induced by retinal neovascularization.
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Xin-Bang
authors.initials: XB
authors.lastname: Mao
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China. Electronic address: yzpengy@163.com.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: You
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000378:metabolism*; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology
chemical_list: D042501:Angiogenic Proteins; D007328:Insulin; D005947:Glucose
keywords: Autophagy; Migration; Neovascularization; Retinal endothelial cells; Sirtuin 3