Transthyretinin repress retinal microvascular endothelial cells under high glucose and hypoxia environment_Chinese Journal of Ocular Fundus Diseases

Authors：

ShaoJun ,  YaoYong

Department of Ophthalmology, Wuxi People′s Hospital, Wuxi 214023, China;

Corresponding author：

YaoYong, Email: pard1@126.com

Keywords：

Retinal Vessels/cytology; Endothelial cells/physiology; Prealbumin/drug effects

DOI：

10.3760/cma.j.issn.1005-1015.2016.02.011

Video：

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Objective To explore transthyretin (TTR) effect on retinal vascular endothelial cells (hREC) under high glucose and hypoxia environment. Methods hREC and human retinal pigment epithelial cell (hRPEC) were cultured at low-glucose (LG), high glucose (HG) and hypoxia. The glucose concentration was increased from 5.5 mmol/L up to 25 mmol/L, and hypoxia was induced by 200 μmol/L CoCl₂. The cells were divided into LG group, LG-hypoxia group, HG group, HG-hypoxia group according to the different cell culture environment. The growth index was detected at 0, 4, 8, 16, 24, 36, 48, 60, 72 hours after cultured. Furthermore, hREC and hRPEC were also cultured with additional TTR (4 μmol/L), respectively. Then transwell co-culture system was employed to reveal the effects of hRPEC on the growth of hREC. Results At 72 hours after cultured, the growth index of hREC and hRPEC in LG group were increased as compared with LG-hypoxia group and HG group (hREC: F=17.098, 22.970; P < 0.05. hRPEC: F=45.442, 9.011; P < 0.05); the growth index of hREC and hRPEC were decreased in HG group and HG-hypoxia group (hREC: F=146.184, P < 0.05；hRPEC: F=27.907, P < 0.05). Additionally, hREC could be significantly repressed by added TTR during culture with high concentration of glucose (F=161.430, 24.106; P < 0.05). hREC could be significantly increased by added TTR during culture with low concentration of glucose (F=200.486, 48.662; P < 0.05). In co-culture process, hRPEC revealed inhibition activity against hREC under both natural and abnormal environment (LG group: F=15.711, P < 0.05; LG-hypoxia group: F=45.659, P < 0.05; HG group: F=7.857, P < 0.05; HG-hypoxia group: F=6.348, P < 0.05). Conclusion Under high glucose and hypoxia environment, the growth of hREC from neovascular could be inhibited by TTR.

Citation： ShaoJun, YaoYong. Transthyretinin repress retinal microvascular endothelial cells under high glucose and hypoxia environment. Chinese Journal of Ocular Fundus Diseases, 2016, 32(2): 159-162. doi: 10.3760/cma.j.issn.1005-1015.2016.02.011 Copy

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9.	Shao J, Xin Y, Yao Y. Correlation of misfolded transthyretin in abnormal vitreous and high myopia related ocular pathologies [J]. Clin Chim Acta,2011, 412(22-23):2117-2121. DOI:10.1016/j.cca.2012.09.006.
10.	Shao J, Xin Y, Yao Y,et al.Functional analysis of misfolded transthyretin extracted from abnormal vitreous with high myopia related ocular pathologies[J]. Clin Chim Acta,2013,415:20-24.DOI:10.1016/j.cca.2012.09.006.
11.	Pullakhandam R,Palika R,Ghosh S,et al.Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: the significance of transthyretin[J].IUBMB Life, 2012,64(12):975-982.DOI:10.1002/iub.1096.
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1. Benson MD.Liver transplantation and transthyretin amyloidosis[J].Muscle Nerve, 2013,47(2):157-162.DOI:10.1002/mus.23521.
2. Pullakhandam R, Palika R, Ghosh S,et al.Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: the significance of transthyretin[J].IUBMB Life, 2012,64(12):975-982.DOI:10.1002/iub.1096.
3. Liz MA, Mar FM, Franquinho F, et al. Aboard transthyretin: Fromtransport to cleavage[J].IUBMB Life, 2010,62(6):429-435.DOI:10.1002/iub.340.
4. 庄淼, 邵珺, 谭澄烨,等.转甲状腺素蛋白对视网膜微血管内皮细胞生物学行为的影响[J].中华眼底病杂志,2015,31(4):368-370.DOI:10.3760/cma.j.issn.1005-1015.2015.04.014.Zhuang M,Shao J,Tan CY, et al.Effects of transthyretin on biological behavior of retinal microvascular epithelial cell[J]. Chin J Ocul Fundus Dis, 2015,31(4):368-370.DOI:10.3760/cma.j.issn.1005-1015.2015.04.014.
5. Hanson ES,Foot LM,Leibold EA.Hypoxia post-translationally activates iron-regulatory protein 2[J].J Biol Chem,1999, 274 (8): 5047-5052.
6. Caltana L, Merelli A, Lazarowski A,et al. Neuronal and glial alterations due to focal cortical hypoxia induced by direct cobalt chloride (CoCl2) brain injection[J]. Neurotox Res,2009,15(4):348-358.DOI: 10.1007/s12640-009-9038-9.
7. Lim YC,Bhatt MP,Kwon MH,et al.Prevention of VEGF-mediated microvascular permeability by C-peptide in diabetic mice[J].Cardiovasc Res, 2014,101(1):155-164. DOI:10.1093/cvr/cvt238.
8. Shao J, Xin Y, Li RX, Fan Y. Vitreous and serum levels of transthyretin (TTR) in high myopia patients are correlated with ocular pathologies [J]. Clin Biochem 2011, 44(8-9): 681-685.DOI:10.1016/j.clinbiochem.2011.03.032.
9. Shao J, Xin Y, Yao Y. Correlation of misfolded transthyretin in abnormal vitreous and high myopia related ocular pathologies [J]. Clin Chim Acta,2011, 412(22-23):2117-2121. DOI:10.1016/j.cca.2012.09.006.
10. Shao J, Xin Y, Yao Y,et al.Functional analysis of misfolded transthyretin extracted from abnormal vitreous with high myopia related ocular pathologies[J]. Clin Chim Acta,2013,415:20-24.DOI:10.1016/j.cca.2012.09.006.
11. Pullakhandam R,Palika R,Ghosh S,et al.Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: the significance of transthyretin[J].IUBMB Life, 2012,64(12):975-982.DOI:10.1002/iub.1096.
12. Lim LS, Lamoureux E, Saw SM,et al.Are myopic eyes less likely to have diabetic retinopathy?[J].Ophthalmology,2010,117(3):524-530.DOI:10.1016/j.ophtha.2009.07. 044.
13. Rani PK, Raman R, Rachapalli SR,et al.Prevalence of refractive errors and associated risk factors in subjects with type 2 diabetes mellitus SN-DREAMS, report 18[J].Ophthalmology,2010,117(6):1155-1162.DOI:10.1016/j.ophtha.2009.10.025.

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Transthyretinin repress retinal microvascular endothelial cells under high glucose and hypoxia environment

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