Inhibition of TRB3 Protects Photoreceptors against Endoplasmic Reticulum Stress-Induced Apoptosis after Experimental Retinal Detachment

Purpose: 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. Conclusion: 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.