机构：[1]Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, China[2]Department of Ophthalmology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China[3]Department of Ophthalmology of Shanghai Tenth People’s Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China[4]Department of Regenerative Medicine and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China[5]Department of Physiology and Pharmacology, Tongji University School of Medicine, Shanghai, China[6]Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China[7]The Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China[8]Department of Ophthalmology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Background: Ceramide plays critical roles in cell proliferation, senescence and apoptosis, and is implicated in neurodegenerative diseases, etc. To clarify if ceramide plays some roles in retinal diseases, we established in vivo and in vitro retinal injury models with ceramide 2 (C2) treatment. In addition, Erythropoietin (EPO), which showed protective effects on retinal cells and blood-retinal barrier (BRB), was also tested for its protection and possible mechanism(s) in these models. Methods: Male Sprague-Dawley rats were divided into four groups, i.e., normal control, vehicle control, C2 treatment, and C2+EPO treatment. After intravitreal injection, the rats were examined for eye fundus, electroretinogram, histological study, and immunostaining, etc. In vitro, retinal neuronal cell line (R28) and the primary human retinal microvascular endothelial cells (HRMECs) were treated with C2, cell viability assay, transendothelial electrical resistance (TEER) and BRB-related molecules were studied to test the protective effect of EPO. Results: Intravitreal C2-treatment caused significant vision loss in rats, as reflected by reduced b-wave amplitude, increased TUNEL positive cells and GFAP immunostaining in retina. Another major retinal injury observed was BRB breakdown following C2-treatment. Such C2-induced injuries were further confirmed by in vitro study. When HRMECs were treated with C2, the TEER was significantly reduced. The mechanisms for C2 to induce such injuries might be through evidently increased expressions of the related molecules like plasmalemma vesicle-associated protein (PLVAP or PV-1), ecto5'-nucleotidase (CD73) and intercellular adhesion molecule-1 (ICAM-1), as observed in C2-treated R28 cells. All these injuries induced by C2 were significantly prevented by EPO both in vivo and in vitro, and its protective mechanisms here might be, in addition to neuroprotective, closely related to its maintenance of BRB integrity, through reducing the expressions of PV-1, CD73 and ICAM-1. Conclusion: C2 could induce severe retinal injury, and such injuries could be effectively prevented by EPO treatment.
基金：
This work was supported by grants obtained
from the Ministry of Science and Technology of
China (2015CB964601, 2016YFA0101302,
2017YFA0104100), National Natural Science
Foundation (81570852, 81670867, 81770942,
31201084), Shanghai Pujiang Program
(15PJ1408700), Shanghai Municipal Commission of
Health and Family Planning Project (201640229),
Shanghai Science and Technology Committee Grant
(17ZR1431300) and the grant from Shanghai East
Hospital (ZJ2014-ZD-002).
第一作者机构：[1]Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Ophthalmology, Renji Hospital, Shanghai Jiaotong University School of Medicine, 160 Pujian Road, Pudong New District, Shanghai 200127, China[*2]Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Outpatient Building, 4th Floor, Room E10, Suzhou 215004, China[*3]Department of Ophthalmology of Shanghai Tenth People’s Hospital and Tongji Eye Institute, Tongji University School of Medicine, 1239 Siping Road, Medical School Building, Room 623, Shanghai 200092, China
推荐引用方式(GB/T 7714)：
H. Lou,D. Kang,Q. Yang,et al.Erythropoietin Protects Retina Against Ceramide 2-Induced Damage in Rat[J].CURRENT MOLECULAR MEDICINE.2017,17(10):699-706.doi:10.2174/1566524018666180322161252.
APA：
H. Lou,D. Kang,Q. Yang,C. Lian,C. Zhang...&J. Zhang.(2017).Erythropoietin Protects Retina Against Ceramide 2-Induced Damage in Rat.CURRENT MOLECULAR MEDICINE,17,(10)
MLA：
H. Lou,et al."Erythropoietin Protects Retina Against Ceramide 2-Induced Damage in Rat".CURRENT MOLECULAR MEDICINE 17..10(2017):699-706
