Altered resting-state brain function in diabetic retinopathy: a meta-analysis of combined transcriptome-neuroimaging study

Abstract

Patients with diabetes may develop cognitive dysfunction, particularly at advanced stages of the disease, manifested by impairments in learning, memory, language, and judgment. Previous studies have reported abnormal brain functional alterations in patients with diabetic retinopathy (DR), which may be associated with cognitive impairment in diabetes; however, the molecular correlates of these brain alterations remain poorly understood. In this study, we performed a coordinate-based neuroimaging meta-analysis to identify convergent resting-state brain functional alterations in patients with DR. By integrating the meta-analytic imaging phenotype with gene-expression data from the Allen Human Brain Atlas, we further conducted spatial transcriptomic -neuroimaging analyses to identify genes whose normative expression patterns were spatially associated with DR-related brain functional alterations. The meta-analysis revealed relatively increased resting-state functional measures in the left cerebellum and corpus callosum, whereas relatively decreased measures were observed in the left calcarine fissure, left middle occipital gyrus, two clusters in the right postcentral gyrus, right anterior cingulate cortex, and right middle temporal gyrus. Functional decoding analyses indicated that these regions were associated with cognitive domains involving language, learning, and cognition. In addition, the regional neuroimaging phenotype was spatially associated with the normative expression patterns of 1,101 genes. Functional enrichment analyses indicated that these genes were enriched in processes related to learning, memory, and cognition, as well as biological processes involving metal ion regulation and cell adhesion. Cell- and tissue-specific enrichment analyses further suggested preferential expression patterns involving retinal and cortical neuronal populations. Collectively, these findings demonstrate convergent resting-state brain functional alterations in patients with DR and reveal their spatial correspondence with normative gene-expression patterns, providing potential insights into the molecular and cellular context of cognitive-related brain alterations associated with DR. https://www.crd.york.ac.uk/prospero/ , identifier CRD420261292056.