Dataset Information

Circadian rhythms in diabetic retinopathy: an overview of pathogenesis and investigational drugs.

ABSTRACT:

Introduction

Circadian rhythm is a natural endogenous process occurring roughly every 24 hours. Circadian rhythm dysfunction is involved in diabetic retinopathy (DR) pathogenesis. Interestingly, there are investigational drugs that exhibit potential in the treatment of DR by targeting circadian rhythm dysfunction.

Areas covered

We performed a literature search in June 2020 using PubMed's Medical Subject Heading (MeSH) terms 'circadian clock,' 'circadian rhythms,' and 'diabetic retinopathy.' This article offers an overview of the physiology of the biological clock and clock regulatory genes and presents an examination of the retinal clock. It discusses the pathogenic mechanisms of DR and emphasizes how circadian rhythm dysfunction at structural, physiological, metabolic and cellular levels, plays a critical role in the development of DR. The latter part of the paper sheds light on those investigational drugs (such as melatonin, tasimelteon and metformin) which exhibit potential in the treatment of DR by the targeting of circadian rhythm dysfunction.

Expert opinion

An enhanced understanding of circadian rhythm and its role in DR could offer therapeutic potential by targeting of circadian rhythm dysfunction.

SUBMITTER: Bhatwadekar AD

PROVIDER: S-EPMC7736502 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDiabetic retinopathy (DR) is a leading cause of vision loss worldwide. Recent studies highlighted the crucial impact of circadian rhythms (CR) on normal retinopathy in response to the external light cues. However, the role of circadian rhythms in DR pathogenesis and potential investigational drugs remains unclear.MethodsTo investigate the weather CR affects DR, differential expression analysis was employed to identify differentially expressed genes (DEGs) from the GEO database (GSE160306). Functional enrichment analysis was conducted to identify relevant signaling pathways. LASSO regression was utilized to screen pivotal genes. Weighted gene co-expression network anlaysis (WGCNA) was applied to identify different modules. Additionally, we use the Comparative Toxicogenomics Database (CTD) database to search key genes related to drugs or molecular compounds. The diabetic mouse model received three consecutive intraperitoneal injections of streptozotocin (STZ) during 3 successive days.ResultsWe initially identified six key genes associated with circadian rhythm in DR, including COL6A3, IGFBP2, IGHG4, KLHDC7A, RPL26P30, and MYL6P4. Compared to normal tissue, the expression levels of COL6A3 and IGFB2 were significantly increased in DR model. Furthermore, we identified several signaling pathways, including death domain binding, insulin-like growth factor I binding, and proteasome binding. We also observed that COL6A3 was positively correlated with macrophages (cor=0.628296895, p=9.96E-08) and Th17 cells (cor=0.665120835, p=9.14E-09), while IGFBP2 showed a negatively correlated with Tgd (cor=-0.459953045, p=0.000247284) and Th2 cells (cor=-0.442269719, p=0.000452875). Finally, we identified four drugs associated with key genes: Resveratrol, Vitamin E, Streptozocin, and Sulindac.ConclusionOur findings revealed several key genes related to circadian rhythms and several relevant drugs in DR, providing a novel insight into the mechanism of DR and potential implications for future DR treatment. This study contributes to a better understanding of CR in DR and its implications for future therapeutic interventions.