The role of endoplasmic reticulum stress in the early stage of diabetic retinopathy.
The aim of this study was to evaluate the role of endoplasmic reticulum (ER) stress in diabetic retinopathy (DR) using in vitro and in vivo models. For the in vivo studies, diabetes was induced in rats, and retinal expression of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and vascular endothelial growth factor (VEGF) in groups of rats at 1, 3, and 6 months was assessed. For the in vitro studies, human retinal capillary endothelial cells (HRCECs) were cultured in the presence of varying glucose concentrations, and the expression of mRNA and protein for GRP78, ATF4, CHOP, and VEGF was assessed. The chosen glucose concentrations were reflective of those apparent in diabetic patients. Expression of VEGF and CHOP mRNA levels were significantly increased in diabetic rats compared to control rats at 1, 3, and 6 months (P < 0.05). In HRCECs cultured in the presence of high as well as variable glucose concentrations, CHOP expression and apoptosis were significantly increased (P < 0.05). However, GRP78 and ATF4 expression levels were unchanged. Our findings suggest that early progression of DR may be mediated by ER stress, but probably does not involve changes in ATF4 or GRP78.
Li
Bin
B
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. scotopsin@yahoo.com.cn
Wang
Hong Sheng
HS
Li
Gui Gang
GG
Zhao
Min Jian
MJ
Zhao
Min Hong
MH
D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000502:physiology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology
D000091342:Endoplasmic Reticulum Chaperone BiP; C051684:GRP78 protein, rat; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP