Exploring metabolomic clues in diabetic retinopathy: a pilot study

with diabetes [1].Prevalence is expected to increase; by 2045, an estimated 160.50 million adults worldwide will be afflicted by DR, and 44.82 million will experience visionthreatening DR [1].Early detection is necessary for reducing DR progression.Despite major risk factors such as hyperglycemia, hypertension, and dyslipidemia, considerable variability in DR onset and progression remains unexplained.This suggests a need to explore pathophysiological mechanisms and biomarker identification.Emerging evidence from metabolomics-the study of small-molecule metabolites in biological systems-has shown promise in uncovering molecular alterations associated with diabetic complications, including DR [2].Previous studies identified metabolites like 12-hydroxyeicosatetraenoic acid (12-HETE) and 3,4-dihydroxybutyrate (3,4-DHBA) as DR-related [2], pointing to inflammation and altered lipid metabolism.However, few studies include healthy controls (HC) in addition to DR and no-DR groups [2].Recognizing the need for more comprehensive designs, this study uses untargeted metabolomics to examine DR, no-DR, and HC groups to identify biomarkers and gain insight into DR pathogenesis. Materials and methodsWe analyzed baseline fasting serum samples from 77 participants aged 40-65 years, drawn from a cohort who had previously enrolled in sleep and circadian rhythm studies conducted at a tertiary academic hospital.Post-illumination pupillary light reflex (PIPR), a measure of intrinsically photosensitive retinal ganglion cells (ipRGCs) located in the inner retina, and nocturnal urinary 6-sulfatoxymelatonin (aMT6s); both previously shown to be reduced in DR, were collected using standardized protocols, previously