RNA interference of GADD153 protects photoreceptors from endoplasmic reticulum stress-mediated apoptosis after retinal detachment

Hong Zhu; Jin Qian; Wenqiu Wang; Quan Yan; Ying Xu; Yuan Jiang; Lei Zhang; Fengqing Lu; Weiting Hu; Xi Zhang; Fenghua Wang; Xiaodong Sun

doi:10.1371/journal.pone.0059339

RNA interference of GADD153 protects photoreceptors from endoplasmic reticulum stress-mediated apoptosis after retinal detachment

Hong Zhu, Jin Qian, Wenqiu Wang, Quan Yan, Ying Xu, Yuan Jiang, Lei Zhang, Fengqing Lu, Weiting Hu, Xi Zhang, Fenghua Wang^*, Xiaodong Sun

^*Corresponding author for this work

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Abstract

Background: Apoptosis of photoreceptors plays a critical role in the vision loss caused by retinal detachment (RD). Pharmacologic inhibition of photoreceptor cell death may prevent RD. This study investigated the role of GADD153 that participates in endoplasmic reticulum (ER) stress-mediated apoptosis of photoreceptor cells after RD. Methods: Retinal detachment was created in Wistar rats by subretinal injection of hyaluronic acid. The rats were then randomly divided into four groups: normal control group, RD group, GADD153 RNAi group and vehicle group. RNA interference of GADD153 was performed using short hairpin RNA (shRNA). Expressions of GADD153 mRNA and protein were examined by RT-PCR and Western blotting analysis, respectively. GADD153 protein distribution in the retinal cells was observed using immunofluorescence confocal laser scanning microscopy. Apoptosis of retinal cells was determined by TdT-mediated fluorescein-16-dUTP nick-end labeling (TUNEL) assay. Results: Lentivirus GADD153 shRNA with the most effective silencing effect was chosen for in vivo animal study and was successfully delivered into the retinal tissues. GADD153 mRNA and protein expressions in GADD153 RNAi group were significantly lower than those in the RD group. Silencing of GADD153 by RNAi protected photoreceptors from ER stress-induced apoptosis. Conclusion: ER stress-mediated pathway is involved in photoreceptor cell apoptosis after RD. GADD153 is a key regulatory molecule regulating ER-stress pathways and plays a crucial role in the apoptosis of photoreceptor cells after RD.

Original language	English
Article number	e59339
Pages (from-to)	1-7
Number of pages	7
Journal	PLoS ONE
Volume	8
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0059339
Publication status	Published - 29 Mar 2013
Externally published	Yes

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Copyright the Author(s) 2013. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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10.1371/journal.pone.0059339Licence: CC BY

Publisher version (open access)Final published version, 1.06 MBLicence: CC BY

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title = "RNA interference of GADD153 protects photoreceptors from endoplasmic reticulum stress-mediated apoptosis after retinal detachment",

abstract = "Background: Apoptosis of photoreceptors plays a critical role in the vision loss caused by retinal detachment (RD). Pharmacologic inhibition of photoreceptor cell death may prevent RD. This study investigated the role of GADD153 that participates in endoplasmic reticulum (ER) stress-mediated apoptosis of photoreceptor cells after RD. Methods: Retinal detachment was created in Wistar rats by subretinal injection of hyaluronic acid. The rats were then randomly divided into four groups: normal control group, RD group, GADD153 RNAi group and vehicle group. RNA interference of GADD153 was performed using short hairpin RNA (shRNA). Expressions of GADD153 mRNA and protein were examined by RT-PCR and Western blotting analysis, respectively. GADD153 protein distribution in the retinal cells was observed using immunofluorescence confocal laser scanning microscopy. Apoptosis of retinal cells was determined by TdT-mediated fluorescein-16-dUTP nick-end labeling (TUNEL) assay. Results: Lentivirus GADD153 shRNA with the most effective silencing effect was chosen for in vivo animal study and was successfully delivered into the retinal tissues. GADD153 mRNA and protein expressions in GADD153 RNAi group were significantly lower than those in the RD group. Silencing of GADD153 by RNAi protected photoreceptors from ER stress-induced apoptosis. Conclusion: ER stress-mediated pathway is involved in photoreceptor cell apoptosis after RD. GADD153 is a key regulatory molecule regulating ER-stress pathways and plays a crucial role in the apoptosis of photoreceptor cells after RD.",

author = "Hong Zhu and Jin Qian and Wenqiu Wang and Quan Yan and Ying Xu and Yuan Jiang and Lei Zhang and Fengqing Lu and Weiting Hu and Xi Zhang and Fenghua Wang and Xiaodong Sun",

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doi = "10.1371/journal.pone.0059339",

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T1 - RNA interference of GADD153 protects photoreceptors from endoplasmic reticulum stress-mediated apoptosis after retinal detachment

AU - Zhu, Hong

AU - Qian, Jin

AU - Wang, Wenqiu

AU - Yan, Quan

AU - Xu, Ying

AU - Jiang, Yuan

AU - Zhang, Lei

AU - Lu, Fengqing

AU - Hu, Weiting

AU - Zhang, Xi

AU - Wang, Fenghua

AU - Sun, Xiaodong

N1 - Copyright the Author(s) 2013. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2013/3/29

Y1 - 2013/3/29

N2 - Background: Apoptosis of photoreceptors plays a critical role in the vision loss caused by retinal detachment (RD). Pharmacologic inhibition of photoreceptor cell death may prevent RD. This study investigated the role of GADD153 that participates in endoplasmic reticulum (ER) stress-mediated apoptosis of photoreceptor cells after RD. Methods: Retinal detachment was created in Wistar rats by subretinal injection of hyaluronic acid. The rats were then randomly divided into four groups: normal control group, RD group, GADD153 RNAi group and vehicle group. RNA interference of GADD153 was performed using short hairpin RNA (shRNA). Expressions of GADD153 mRNA and protein were examined by RT-PCR and Western blotting analysis, respectively. GADD153 protein distribution in the retinal cells was observed using immunofluorescence confocal laser scanning microscopy. Apoptosis of retinal cells was determined by TdT-mediated fluorescein-16-dUTP nick-end labeling (TUNEL) assay. Results: Lentivirus GADD153 shRNA with the most effective silencing effect was chosen for in vivo animal study and was successfully delivered into the retinal tissues. GADD153 mRNA and protein expressions in GADD153 RNAi group were significantly lower than those in the RD group. Silencing of GADD153 by RNAi protected photoreceptors from ER stress-induced apoptosis. Conclusion: ER stress-mediated pathway is involved in photoreceptor cell apoptosis after RD. GADD153 is a key regulatory molecule regulating ER-stress pathways and plays a crucial role in the apoptosis of photoreceptor cells after RD.

AB - Background: Apoptosis of photoreceptors plays a critical role in the vision loss caused by retinal detachment (RD). Pharmacologic inhibition of photoreceptor cell death may prevent RD. This study investigated the role of GADD153 that participates in endoplasmic reticulum (ER) stress-mediated apoptosis of photoreceptor cells after RD. Methods: Retinal detachment was created in Wistar rats by subretinal injection of hyaluronic acid. The rats were then randomly divided into four groups: normal control group, RD group, GADD153 RNAi group and vehicle group. RNA interference of GADD153 was performed using short hairpin RNA (shRNA). Expressions of GADD153 mRNA and protein were examined by RT-PCR and Western blotting analysis, respectively. GADD153 protein distribution in the retinal cells was observed using immunofluorescence confocal laser scanning microscopy. Apoptosis of retinal cells was determined by TdT-mediated fluorescein-16-dUTP nick-end labeling (TUNEL) assay. Results: Lentivirus GADD153 shRNA with the most effective silencing effect was chosen for in vivo animal study and was successfully delivered into the retinal tissues. GADD153 mRNA and protein expressions in GADD153 RNAi group were significantly lower than those in the RD group. Silencing of GADD153 by RNAi protected photoreceptors from ER stress-induced apoptosis. Conclusion: ER stress-mediated pathway is involved in photoreceptor cell apoptosis after RD. GADD153 is a key regulatory molecule regulating ER-stress pathways and plays a crucial role in the apoptosis of photoreceptor cells after RD.

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RNA interference of GADD153 protects photoreceptors from endoplasmic reticulum stress-mediated apoptosis after retinal detachment

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