Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Aug 9:16:957667.
doi: 10.3389/fnins.2022.957667. eCollection 2022.

Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy

Chengzhi Liu  1   2 , Wenkang Dong  2 , Zhengshuai Lv  1 , Li Kong  2 , Xiang Ren  2
Affiliations
Review

Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy

Chengzhi Liu et al. Front Neurosci. .

Abstract

Diabetic retinopathy (DR) is a common complication of diabetes mellitus and has been considered a microvascular disease for a long time. However, recent evidence suggests that diabetic retinal neurodegeneration (DRN), which manifests as neuronal apoptosis, a decrease in optic nerve axons, and reactive gliosis, occurs prior to retinal microvascular alterations. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of thioredoxin (Trx), and it acts by inhibiting its reducing capacity, thereby promoting cellular oxidative stress. In addition, it participates in regulating multiple signaling pathways as a member of the α-arrestin family of proteins. Accumulating evidence suggests that TXNIP is upregulated in diabetes and plays a pivotal role in the pathophysiological process of DR. In this review, we summarized the role of TXNIP in DRN, aiming to provide evidence for DR treatment in the future.

Keywords: TXNIP (thioredoxin-interacting protein); TXNIP modulators; diabetic retinal neurodegeneration; diabetic retinopathy; thioredoxin.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of thioredoxin-interacting protein (TXNIP) being regulated in diabetes and contributing to the pathogenesis of DRN. (A) Mechanism of TXNIP regulation at the translational level. (B) Mechanism of TXNIP regulation at the post-translational level. (C) TXNIP participates in different signaling pathways to promote DRN.
See this image and copyright information in PMC

References

    1. Abdelsaid M. A., Matragoon S., Ergul A., El-Remessy A. B. (2014). Deletion of thioredoxin interacting protein (TXNIP) augments hyperoxia-induced vaso-obliteration in a mouse model of oxygen induced-retinopathy. PLoS One 9:e110388. 10.1371/journal.pone.0110388 - DOI - PMC - PubMed
    1. Adornetto A., Gesualdo C., Laganà M. L., Trotta M. C., Rossi S., Russo R. (2021). Autophagy: a novel pharmacological target in diabetic retinopathy. Front. Pharmacol. 12:695267. 10.3389/fphar.2021.695267 - DOI - PMC - PubMed
    1. Al-Gayyar M. M., Abdelsaid M. A., Matragoon S., Pillai B. A., El-Remessy A. B. (2011). Thioredoxin interacting protein is a novel mediator of retinal inflammation and neurotoxicity. Br. J. Pharmacol. 164 170–180. 10.1111/j.1476-5381.2011.01336.x - DOI - PMC - PubMed
    1. Antonetti D. A., Silva P. S., Stitt A. W. (2021). Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat. Rev. Endocrinol. 17 195–206. 10.1038/s41574-020-00451-4 - DOI - PMC - PubMed
    1. Ao H., Li H., Zhao X., Liu B., Lu L. (2021). TXNIP positively regulates the autophagy and apoptosis in the rat müller cell of diabetic retinopathy. Life Sci. 267:118988. 10.1016/j.lfs.2020.118988 - DOI - PubMed

LinkOut - more resources