2. Academic Validation
  3. Thioredoxin upregulation delays diabetes-induced photoreceptor cell degeneration via AMPK-mediated autophagy and exosome secretion

Thioredoxin upregulation delays diabetes-induced photoreceptor cell degeneration via AMPK-mediated autophagy and exosome secretion

  • Diabetes Res Clin Pract. 2022 Mar;185:109788. doi: 10.1016/j.diabres.2022.109788.
Xiang Ren 1,  Jinjuan Lv 1,  Nina Wang 1,  Jiasu Liu 2,  Chuanzhou Gao 1,  Xiaoli Wu 1,  Yang Yu 1,  Qiufeng Teng 1,  Wenkang Dong 1,  Hui Kong 3,  Li Kong 4
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China.
  • 2 Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China; The Second Hospital of Dalian Medical University, Dalian 116023, LiaoNing Province, China.
  • 3 The Second Hospital of Dalian Medical University, Dalian 116023, LiaoNing Province, China. Electronic address: [email protected].
  • 4 Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China. Electronic address: [email protected].
PMID: 35182712 DOI: 10.1016/j.diabres.2022.109788
Abstract

Aims: Autophagy and exosome secretion in photoreceptor and RPE cells play an important role during diabetic retinopathy (DR). Thioredoxin (Trx) upregulation delays diabetes-induced photoreceptor cell degeneration, which the effect of Autophagy and exosome secretion on it is unclear. Therefore, we investigated the effect of them on Trx upregulation to delay diabetes-induced photoreceptor cell degeneration and to identify the potential therapy for DR in the future.

Methods: Trx-transgenic mice and 661w cell were as models. Retinal function and morphology were evaluated by electroretinography and H&E staining. TUNEL staining was used to evaluate Apoptosis. The protein expression was detected by Western blotting. TEM and mRFP-GFP-LC3 method were used to analyze Autophagy.

Results: In vitro and in vivo, Trx upregulation can delay diabetes-induced photoreceptor cell degeneration. Moreover, the expression of LC3 and p62 was decreasing and the expression of Alix and CD63 was increasing after Trx overexpression. However, it was inhibited after AMPK Inhibitor treatment. Additionally, secreted exosomes from photoreceptor were phagocytosed by RPE cells to regulate its physiological function.

Conclusions: Trx upregulation can delay diabetes-induced photoreceptor cell degeneration via AMPK-mediated Autophagy and exosome secretion. Secreted exosomes from photoreceptor cells could be phagocytosed and degraded by RPE cells in DR.

Keywords

Autophagy; Diabetic retinopathy; Exosomes; Photoreceptor; Thioredoxin.

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