Purpose: To study the effect of autophagy on vitality, migration, and tube formation of RF/6A cells under the condition of D-glucose. Methods: Cultured RF/6A cells were randomly divided into 4 groups (control, low glucose, high glucose, and high glucose with 3-methyladenine [3-MA]). Autophagy-related proteins (Atg7, p62, and LC3) were monitored. Cell vitality, cell migration, tube formation, reactive oxygen species (ROS) production, and apoptosis were assessed. Results: Cell vitality significantly decreased and cell migration and tube formation significantly increased in the high-glucose group (p < 0.05). Pretreatment with 3-MA significantly increased cell viability and inhibited cell migration and tube formation (p < 0.05). ROS production increased in the high-glucose group and decreased in the high-glucose with N-acetylcysteine (NAC) group (p < 0.05). The level of apoptosis increased in the high-glucose group, while it was reduced in the high-glucose with 3-MA group. Conclusion: Autophagy maybe participates in the formation of retinal neovascularization induced by high glucose.

1.
Negi A, Vernon SA: An overview of the eye in diabetes. J R Soc Med 2003;96:266-272.
2.
Tielsch JM, Sommer A, Witt K, Katz J, Royall RM: Blindness and visual impairment in an American urban population. The Baltimore Eye Survey. Arch Ophthalmol 1990;108:286-290.
3.
Burgess PI, MacCormick IJ, Harding SP, Bastawrous A, Beare NA, Garner P: Epidemiology of diabetic retinopathy and maculopathy in Africa: a systematic review. Diabet Med 2013;30:399-412.
4.
Kolluru GK, Bir SC, Kevil CG: Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med 2012;2012:918267.
5.
Carmeliet P: Angiogenesis in health and disease. Nat Med 2003;9:653-660.
6.
Folkman J: Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 2007;6:273-286.
7.
Ahn A, Frishman WH, Gutwein A, Passeri J, Nelson M: Therapeutic angiogenesis: a new treatment approach for ischemic heart disease - part II. Cardiol Rev 2008;16:219-229.
8.
Ahn A, Frishman WH, Gutwein A, Passeri J, Nelson M: Therapeutic angiogenesis: a new treatment approach for ischemic heart disease - part I. Cardiol Rev 2008;16:163-171.
9.
Du J, Teng RJ, Guan T, Eis A, Kaul S, Konduri GG, Shi Y: Role of autophagy in angiogenesis in aortic endothelial cells. Am J Physiol Cell Physiol 2012;302:C383-C391.
10.
Ramakrishnan S, Nguyen TM, Subramanian IV, Kelekar A: Autophagy and angiogenesis inhibition. Autophagy 2007;3:512-515.
11.
Gottlieb RA, Mentzer RM: Autophagy during cardiac stress: joys and frustrations of autophagy. Annu Rev Physiol 2010;72:45-59.
12.
Gonzalez CD, Lee MS, Marchetti P, Pietropaolo M, Towns R, Vaccaro MI, Watada H, Wiley JW: The emerging role of autophagy in the pathophysiology of diabetes mellitus. Autophagy 2011;7:2-11.
13.
Liu H, Yu S, Zhang H, Xu J: Angiogenesis impairment in diabetes: role of methylglyoxal-induced receptor for advanced glycation endproducts, autophagy and vascular endothelial growth factor receptor 2. PLoS One 2012;7:e46720.
14.
Crawford TN, Alfaro DV 3rd, Kerrison JB, Jablon EP: Diabetic retinopathy and angiogenesis. Curr Diabetes Rev 2009;5:8-13.
15.
Bhattacharyya S, Sul K, Krukovets I, Nestor C, Li J, Adognravi OS: Novel tissue-specific mechanism of regulation of angiogenesis and cancer growth in response to hyperglycemia. J Am Heart Assoc 2012;1:e005967.
16.
Garcia NA, Ontoria-Oviedo I, González-King H, Diez-Juan A, Sepúlveda P: Glucose starvation in cardiomyocytes enhances exosome secretion and promotes angiogenesis in endothelial cells. PLoS One 2015;10:e0138849.
17.
Ma T, Zhu J, Chen X, Zha D, Singhal PC, Ding G: High glucose induces autophagy in podocytes. Exp Cell Res 2013;319:779-789.
18.
Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al: Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012;8:445-544.
19.
Tanaka Y, Kume S, Kitada M, Kanasaki K, Uzu T, Maegawa H, Koya D: Autophagy as a therapeutic target in diabetic nephropathy. Exp Diabetes Res 2012;2012:628978.
20.
Yu Y, Duan J, Yu Y, Li Y, Liu X, Zhou X, Ho KF, Tian L, Sun Z: Silica nanoparticles induce autophagy and autophagic cell death in HepG2 cells triggered by reactive oxygen species. J Hazard Mater 2014;270:176-186.
21.
Tran AT, Ramalinga M, Kedir H, Clarke R, Kumar D: Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells. Eur J Nutr 2015;54:265-272.
22.
Rosen R, Vagaggini T, Chen Y, Hu DN: Zeaxanthin inhibits hypoxia-induced VEGF secretion by RPE cells through decreased protein levels of hypoxia-inducible factors-1α. Biomed Res Int 2015;2015:687386.
23.
Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A: DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol 2002;157:455-468.
24.
Bernales S, McDonald KL, Walter P: Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol 2006;4:e423.
25.
Nishida K, Yamaguchi O, Otsu K: Crosstalk between autophagy and apoptosis in heart disease. Circ Res 2008;103:343-351.
26.
Yang Z, Mo X, Gong Q, Pan Q, Yang X, Cai W, Li C, Ma JX, He Y, Gao G: Critical effect of VEGF in the process of endothelial cell apoptosis induced by high glucose. Apoptosis 2008;13:1331-1343.
27.
Piano I, Novelli E, Della Santina L, Strettoi E, Cervetto L, Gargini C: Involvement of autophagic pathway in the progression of retinal degeneration in a mouse model of diabetes. Front Cell Neurosci 2016;10:42.
28.
Fu D, Yu JY, Yang S, Wu M, Hammad SM, Connell AR, Du M, Chen J, Lyons TJ: Survival or death: a dual role for autophagy in stress-induced pericyte loss in diabetic retinopathy. Diabetologia 2016;59:2251-2261.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.