Approved Research

To explore the role and underlying mechanisms of circadian rhythm in the development and progression of diabetic retinopathy (DR)

Lay summary

Aims: To determine the impact of circadian disruption in the development and progression of diabetic retinopathy (DR). And to investigate the possible mechanisms underlying the association between circadian rhythm and DR.

Scientific rationale: DR is the leading cause of preventable vision loss in working population worldwide, and its prevalence remains climbing with growing numbers of diabetes worldwide. Circadian rhythms are a series of behavioral and physiological processes in response to light-dark cycle, and its dysfunction due to sleep/wake disturbance have a strong correlation with eye health and metabolic syndrome through a variety of physiobiological pathways. Therefore, we aim to investigate whether and how circadian rhythmicity interact with the development and progression of DR. Furthermore, the underlying mechanism will be explored through multivariable linear/logistic regression, mediator analysis, and machine learning methods.

Project duration: 36 months.

Scope extension:

The overall aim of this project is to determine the role of circadian rhythm in the development and progression of DR, and elucidate its underlying mechanisms.

Specific aims:

1. To determine the impact of circadian disruption in the development and progression of DR.
2. To investigate the possible mechanism underlying the association between circadian rhythm and DR.

New Scope and additional work:

We propose to extend the scope to include a broader range of blinding eye diseases and specific cardiometabolic disorders such as cardiovascular diseases, type 2 diabetes, and hyperuricemia. Therefore, the overall aim of this project is to investigate the common and unique risk factors in the development and progression of blinding eye diseases and cardiometabolic health.

Specific aims:

1. To assess the association between circadian rhythm and the primary causes for blindness or moderate-to-severe visual impairment in late life.
2. To investigate the bi-directional association between blinding eye conditions and cardiometabolic disorders, including cardiovascular diseases, type 2 diabetes, and hyperuricemia, etc.
3. To identify common and distinct modifiable risk factors for both blinding eye diseases and cardiometabolic disorders.

4. To explore the underlying pathophysiological and genetic mechanisms.

Public health impact: This project will benefit millions of people with diabetes with or without DR globally. If risk factors related to circadian rhythms for DR are confirmed, then circadian rhythmicity may provide promising intervention targets and will open new opportunities for the prevention and management of DR.