Oncotarget

Research Papers:

Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice

Xiang Ren, Chen Li, Junli Liu, Chenghong Zhang, Yuzhen Fu, Nina Wang, Haiying Ma, Heyuan Lu, Hui Kong and Li Kong _

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Oncotarget. 2017; 8:61350-61364. https://doi.org/10.18632/oncotarget.18134

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Abstract

Xiang Ren1,*, Chen Li1,*, Junli Liu1, Chenghong Zhang1, Yuzhen Fu1, Nina Wang1, Haiying Ma1, Heyuan Lu1, Hui Kong2 and Li Kong1

1Department of Histology and Embryology, Dalian Medical University, Dalian 116044, Liaoning Province, China

2Department of Otorhinolaryngology, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China

*These authors have contributed equally to this work

Correspondence to:

Li Kong, email: kongli@dmu.edu.cn

Hui Kong, email: konghui6905@163.com

Keywords: thioredoxin, diabetes, retina, apoptosis, sulforaphane

Received: March 01, 2017     Accepted: April 11, 2017     Published: May 24, 2017

ABSTRACT

Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new therapeutic targets for the clinical treatment and prevention of DR. For in vivo studies, a high-fat diet and streptozotocin (STZ) injection were used to generate the diabetes model. Hematoxylin-eosin staining was used for morphological observations and measurements of the outer nuclear layer thickness. Electroretinography (ERG) was used to assess retinal function. For in vitro studies, Neuro2a cells were incubated in normal (5.5 mM) and high-glucose (30 mM) conditions. Flow cytometry assays were performed to analyze apoptosis. Additionally, real-time PCR and Western blotting analyses were carried out to determine gene and protein expression in vitro and in vivo. Taken together, the results indicated that retinal neuropathy occurred prior to endothelial damage induced by diabetes, and thioredoxin (Trx) plays a key role in this process. This underlying mechanism may be related to activation of the Trx/ASK1/p-p38/Trx-interacting protein pathway.


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