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Hong Zhu, Quan Yan, Fenghua Wang, Xueting Luo, Xiaodong Sun; NOX2 induces photoreceptor apoptosis through endoplasmic reticulum stress pathway in a rat model of retinal detachment. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5375.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the expression of NOX2, a NADPH oxidase, and its regulation on endoplasmic reticulum stress (ERS)-mediated apoptosis and photoreceptor damage using a rat model of retinal detachment (RD).
Animal model of RD was created in Brown Norway rats by subretinal injection of 1% sodium hyaluronate. Lentivirus NOX2 shRNA (LV-NOX2-sh) was constructed to inhibit NOX2 expression in vivo. The rats were randomly divided into four groups: normal control group (non-detachment), RD control group, negative control group (vehicle+RD) and LV-NOX2-sh+RD group. Expression of NOX2 and biomarkers of ERS pathway (CHOP, TRB3 and Caspase-12) were detected using quantitative real-time PCR and western blotting on day 1, 3, 5 and 7 after RD in each group. Non-detachment animals served as control. TdT-mediated fluorescein-16-dUTP nick-end labeling (TUNEL) assay was used to stain the apoptosis cells in histological sections. Retinal outer nuclear layer (ONL) thickness was measured to assess retina damage in each group.
NOX2 expression was significantly increased after RD. CHOP and TRB3 were over-expressed in RD control group. In LV-NOX2-sh group, the expression of NOX2 was notably inhibited in vivo. And the expressions of CHOP and TRB3 were decreased compared with those RD rats and vehicle+RD rats at the same time points. The ratio of TUNEL-positive photoreceptors in LV-NOX2-sh+RD group was significantly reduced accompany with less expression of Caspase-12. Meanwhile, the ONL thickness in LV-NOX2-sh+RD group was thicker than that both in RD group and vehicle+RD group.
NOX2 expression is up-regulated in retinas and induces ERS pathway after RD. Inhibition of NOX2 protects photoreceptors through ERS-mediated apoptosis pathway in RD rat model. NOX2 may be a crucial regulatory molecule in ERS-mediated photoreceptor apoptosis after RD.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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