# Sleep and Circadian Regulation in Diabetic Retinopathy: The Role of Intrinsically Photosensitive Retinal Ganglion Cells and Melatonin Supplementation

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $665,057

## Abstract

PROJECT SUMMARY
Diabetes affects more than 30 million people in the United States, with 90-95% having type 2 diabetes. Diabetic
retinopathy, one of the most serious complications of diabetes, is the leading cause of blindness. While diet,
exercise and medications have been cornerstones of diabetes treatment to control glucose levels, the influence
of sleep and circadian regulation on metabolic control are increasingly recognized as potential targets of future
preventive treatment strategies. Recent work discovered that there is a dysfunction of the melanopsin-expressing
intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with diabetic retinopathy. These ipRGCs
are a crucial part of entraining (synchronizing) the circadian system, which influences melatonin secretion and
regulates sleep/wake timing and metabolic physiology. Recent data indicate that individuals with diabetic
retinopathy show abnormalities in ipRGC function and abnormal melatonin physiology. The novel hypothesis
we propose to test is that ipRGC dysfunction associated with type 2 diabetes and diabetic retinopathy leads to
disturbances in sleep and circadian regulation, which further adversely affects their metabolic control and could
accelerate disease progression. Further, we hypothesize that melatonin supplementation will disrupt this vicious
cycle. The proposed study will comprehensively examine ipRGC function via pupillometry in patients with type 2
diabetes with and without diabetic retinopathy. These groups will provide a range of ipRGC function. Sleep
duration and quality (via wrist actigraphy), at-home electroencephalography (EEG), polysomnography, nocturnal
melatonin secretion (measured from urinary 6-sulfatoxymelatonin), circadian regulation (24-hour blood sampling
for melatonin and cortisol) and standard metabolic outcomes (hemoglobinA1c, fasting glucose, 24-hour mean
glucose levels from continuous glucose monitoring) will be the outcomes and examined as a function of ipRGC
function. Then, patients with diabetic retinopathy will be randomized to receive nightly melatonin
supplementation or placebo for 8 weeks. The primary outcomes will be assessed at the end of the study which
include sleep as measured by actigraphy and circadian regulation as assessed by 24-hour hormone sampling.
Glucose parameters will also be assessed (hemoglobinA1c, fasting glucose, 24-hour mean glucose levels from
continuous glucose monitoring). The proposed study will advance our understanding of the relationship between
ipRGC function and the nonvisual health of people with diabetes, and provide evidence of potential benefits of
melatonin in patients with diabetic retinopathy. These data will be highly relevant given the current epidemic of
diabetes and diabetic retinopathy, and will inform potential therapeutic interventions, leading to improve disease
outcomes in these patients.

## Key facts

- **NIH application ID:** 10701729
- **Project number:** 5R01EY029782-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Sirimon Reutrakul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $665,057
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701729

## Citation

> US National Institutes of Health, RePORTER application 10701729, Sleep and Circadian Regulation in Diabetic Retinopathy: The Role of Intrinsically Photosensitive Retinal Ganglion Cells and Melatonin Supplementation (5R01EY029782-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10701729. Licensed CC0.

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