title: Inhibition of TRB3 Protects Photoreceptors against Endoplasmic Reticulum Stress-Induced Apoptosis after Experimental Retinal Detachment.
abstract: OBJECTIVE
  To investigate the expression of tribbles homologue 3 (TRB3) and its regulation on endoplasmic reticulum stress (ERS)-induced photoreceptor apoptosis after retinal detachment (RD) using a rat model.
  
  
  METHODS
  RD animal model was created in Wistar rats by subretinal injection of 1% sodium hyaluronate. At various time points after RD, expression of TRB3 was detected by quantitative real-time PCR and Western blotting. TRB3 protein distribution in retina was evaluated by immunohistochemistry. RNA interference was used to inhibit TRB3 expression and subretinal injection of lentivirus TRB3 shRNA (LV-TRB3-sh) was performed. The rats were then randomly divided into four groups: normal control group, RD group, vehicle + RD group and LV-TRB3-sh + RD group. The mRNA and protein level of TRB3 as well as Caspase-12 were detected. TdT-mediated fluorescein-16-dUTP nick-end labeling (TUNEL) assay was used to detect the apoptosis of retinal cells. Retinal outer nuclear layer (ONL) thickness was measured to assess retina damage in each group.
  
  
  RESULTS
  TRB3 expression and TRB3-positive cell count were significantly increased after RD and peaked at day 3 after RD. The ratio of TUNEL-positive photoreceptors and expression of ERS-induced apoptosis marker Caspase-12 in LV-TRB3-sh + RD group were significantly reduced. The ONL thickness in LV-TRB3-sh + RD group was thicker than that both in RD group and vehicle + RD group.
  
  
  CONCLUSIONS
  TRB3 expression is up-regulated in retinas after RD and knockdown of TRB3 protects photoreceptors against ERS-induced apoptosis. TRB3 may be a crucial molecule in photoreceptor apoptosis induced by ERS after RD.
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .
authors: Quan
authors: Q
authors: Yan
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .
authors: Hong
authors: H
authors: Zhu
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .|b Shanghai Key Laboratory of Fundus Disease , Shanghai , China and.
authors: Feng-Hua
authors: FH
authors: Wang
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .
authors: Jing-Yang
authors: JY
authors: Feng
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .
authors: Wen-Qiu
authors: WQ
authors: Wang
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .
authors: Xiang
authors: X
authors: Shi
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .
authors: Yan-Ping
authors: YP
authors: Zhou
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .|c Eye Research Institute of Shanghai JiaoTong University , Shanghai , China.
authors: Xi
authors: X
authors: Zhang
authors: a Department of Ophthalmology , Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University , Shanghai , China .|c Eye Research Institute of Shanghai JiaoTong University , Shanghai , China.
authors: Xiao-Dong
authors: XD
authors: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053454:Caspase 12 / Q000235:genetics; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005822:Genetic Vectors; D006820:Hyaluronic Acid; D020287:In Situ Nick-End Labeling; D016086:Lentivirus / Q000235:genetics; D008297:Male; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012163:Retinal Detachment / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; C502443:Trib3 protein, rat; D006820:Hyaluronic Acid; D017346:Protein Serine-Threonine Kinases; D053454:Caspase 12
keywords: Apoptosis; TRB3; endoplasmic reticulum stress; photoreceptor; retinal detachment