Ubiquitin-proteasome system in diabetic retinopathy

Zane Svikle; Beate Peterfelde; Nikolajs Sjakste; Kristine Baumane; Rasa Verkauskiene; Chi-Juei Jeng; Jelizaveta Sokolovska

doi:10.7717/peerj.13715

Ubiquitin-proteasome system in diabetic retinopathy

PeerJ. 2022 Jul 19:10:e13715. doi: 10.7717/peerj.13715. eCollection 2022.

Authors

Zane Svikle¹, Beate Peterfelde^{1

2}, Nikolajs Sjakste¹, Kristine Baumane^{1

2}, Rasa Verkauskiene³, Chi-Juei Jeng^{4

5}, Jelizaveta Sokolovska¹

Affiliations

¹ Faculty of Medicine, University of Latvia, Riga, Latvia.
² Ophthalmology Department, Riga East University Hospital, Riga, Latvia.
³ Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁴ Ophthalmology Department, Taipei Medical University Shuang Ho Hospital, Ministry of Health and Welfare, Taipei, The Republic of China (Taiwan).
⁵ College of Medicine, Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

Diabetic retinopathy (DR) is the most common complication of diabetes, being the most prevalent reason for blindness among the working-age population in the developed world. Despite constant improvement of understanding of the pathogenesis of DR, identification of novel biomarkers of DR is needed for improvement of patient risk stratification and development of novel prevention and therapeutic approaches. The ubiquitin-proteasome system (UPS) is the primary protein quality control system responsible for recognizing and degrading of damaged proteins. This review aims to summarize literature data on modifications of UPS in diabetes and DR. First, we briefly review the structure and functions of UPS in physiological conditions. We then describe how UPS is involved in the development and progression of diabetes and touch upon the association of UPS genetic factors with diabetes and its complications. Further, we focused on the effect of diabetes-induced hyperglycemia, oxidative stress and hypoxia on UPS functioning, with examples of studies on DR. In other sections, we discussed the association of several other mechanisms of DR (endoplasmic reticulum stress, neurodegeneration etc) with UPS modifications. Finally, UPS-affecting drugs and remedies are reviewed. This review highlights UPS as a promising target for the development of therapies for DR prevention and treatment and identifies gaps in existing knowledge and possible future study directions.

Keywords: Diabetes; Diabetic eye disease; Retinopathy; Ubiquitin-proteasome system.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytoplasm / metabolism
Diabetes Mellitus, Experimental* / drug therapy
Diabetic Retinopathy* / etiology
Humans
Proteasome Endopeptidase Complex / metabolism
Ubiquitin / metabolism

Substances

Proteasome Endopeptidase Complex
Ubiquitin

Grants and funding

The work was supported by the project of the Mutual funds Taiwan-Latvia-Lithuania “Novel biomarkers of diabetic retinopathy: epigenetic modifications of genes of ubiquitin-proteasome system, telomere length and proteasome concentration” and a fundamental research grant in Biomedicine and Pharmacy “Research of biomarkers and natural substances for acute and chronic diseases’ diagnostics and personalized treatment” by the Faculty of Medicine, University of Latvia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.