title: 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.
authors.affiliation: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Delong
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ju
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, 264003 P. R. China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Liying
authors.initials: L
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Qishan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, Weifang Medical University, Weifang, 261053 P. R. China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Mi
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, 264003 P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Chunsik
authors.initials: C
authors.lastname: Lee
authors.affiliation: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D052157:Aptamers, Nucleotide / Q000633:toxicity; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D008810:Mice, Inbred C57BL; D051381:Rats; D012164:Retinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D042561:Vascular Endothelial Growth Factor B / Q000008:administration & dosage*
chemical_list: D052157:Aptamers, Nucleotide; D042561:Vascular Endothelial Growth Factor B; C495058:pegaptanib