The long-range and short-range functional connectivity density of diabetic retinopathy and their spatial relationships with gene expression and neurotransmitters.

Objective: This study explores the changes in functional connectivity density (FCD) among patients with diabetic retinopathy and its associations with gene expression and the distribution of neurotransmitter density, aiming to elucidate potential pathophysiological mechanisms underlying diabetic retinopathy.

Methods: This study investigates changes in short-range functional connectivity density (sFCD) within regions and long-range functional connectivity density (lFCD) between regions in 46 patients with diabetic retinopathy compared with 46 healthy controls. In addition, we examine the relationship between FCD changes in patients with diabetic retinopathy and whole-brain gene expression through partial least squares (PLS) regression and functional enrichment analysis of PLS-weighted genes. Finally, we assess the spatial correlation between abnormal FCD patterns and neurotransmitter density distribution using correlation analysis.

Results: The patients with diabetic retinopathy show a reduction in lFCD in the left inferior occipital gyrus and in the cortex surrounding the left calcarine fissure (left Cal) and a significant decrease in sFCD in the left Cal and the supplementary motor area (SMA). Furthermore, FCD is significantly positively correlated with the PLS1 gene and exhibits notable associations with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the abnormal FCD patterns in patients with diabetic retinopathy demonstrate a significant spatial correlation with the density of 5HT1A and CB1 receptors.

Conclusion: In summary, patients with diabetic retinopathy have different degrees of abnormal brain connectivity function in vision-related and SMA regions, and this abnormal performance may be related to the high oxidative stress state and neurovascular abnormalities present in patients with diabetic retinopathy.