Zhong Yu-Lin, Liu Hao, Huang Xin
Department of Ophthalmology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China.
School of Ophthalmology and Optometry, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Front Cell Neurosci. 2025 Apr 10;19:1476038. doi: 10.3389/fncel.2025.1476038. eCollection 2025.
Diabetic retinopathy (DR) is a condition characterized by fundus lesions resulting from retinal microvascular leakage and obstruction linked to chronic progressive diabetes mellitus. Previous neuroimaging research has revealed both structural and functional changes in the brains of DR patients. Nevertheless, the variations in dynamic functional connectivity density (dFCD) within the brains of DR patients, along with the underlying molecular mechanisms connected to these changes, have yet to be fully understood.
Forty-seven diabetic retinopathy (DR) patients and 46 healthy controls (HCs) matched for sex, age, and education were recruited for this study from the Department of Ophthalmology at the Jiangxi Provincial People's Hospital. All subjects underwent resting-state functional magnetic resonance imaging scans to analyze the differences in dFCD between the two groups. Utilizing the Allen Human Brain Atlas, we conducted spatial correlation analyses integrating transcriptomic and neuroimaging data to pinpoint genes showing correlated expression levels with dFCD alterations in DR patients. Subsequently, we carried out gene enrichment, specific expression, and protein-protein interaction analyses.
In comparison to the HC group, the DR group exhibited significantly reduced dFCD variability in the left anterior cingulum, left superior occipital gyrus, and right postcentral gyrus. The abnormal dFCD variability is linked to 1,318 positively and 1,318 negatively associated genes, primarily enriched for biological functions such as ion channels, synapses, and cellular junctions. Specific expression analysis revealed that these genes were distinctly expressed in Purkinje neurons, cortex, and striatum brain regions. Furthermore, protein-protein interaction (PPI) analyses indicated that these positive and negative genes could organize PPI networks with the support of respective hub genes.
our study identified altered dFCD variability in brain regions linked to visual and cognitive functions in DR patients. Moreover, transcriptome-neuroimaging correlation analyses revealed a spatial association between these dFCD changes and the genes with unique functional profiles. These genes were enriched in biologically significant functions and pathways, specific to certain cells and brain areas. Our research offers novel understandings of the genetic mechanisms influencing dFCD alterations in DR.
糖尿病视网膜病变（DR）是一种以眼底病变为特征的疾病，其由与慢性进行性糖尿病相关的视网膜微血管渗漏和阻塞引起。先前的神经影像学研究已经揭示了DR患者大脑中的结构和功能变化。然而，DR患者大脑内动态功能连接密度（dFCD）的变化以及与这些变化相关的潜在分子机制尚未完全清楚。
从江西省人民医院眼科招募了47例糖尿病视网膜病变（DR）患者和46例在性别、年龄和教育程度上匹配的健康对照（HC）。所有受试者均接受静息态功能磁共振成像扫描，以分析两组之间dFCD的差异。利用艾伦人类脑图谱，我们进行了整合转录组学和神经影像学数据的空间相关性分析，以确定与DR患者dFCD改变显示出相关表达水平的基因。随后，我们进行了基因富集、特异性表达和蛋白质-蛋白质相互作用分析。
与HC组相比，DR组在左侧前扣带回、左侧枕上回和右侧中央后回的dFCD变异性显著降低。异常的dFCD变异性与1318个正相关基因和1318个负相关基因有关，主要富集于离子通道、突触和细胞连接等生物学功能。特异性表达分析表明，这些基因在浦肯野神经元、皮层和纹状体脑区有明显表达。此外，蛋白质-蛋白质相互作用（PPI）分析表明，这些正、负基因可以在各自枢纽基因的支持下组织PPI网络。
我们的研究确定了DR患者中与视觉和认知功能相关的脑区dFCD变异性改变。此外，转录组-神经影像学相关性分析揭示了这些dFCD变化与具有独特功能特征的基因之间的空间关联。这些基因富集于对某些细胞和脑区具有特异性的生物学重要功能和途径。我们的研究为影响DR中dFCD改变的遗传机制提供了新的认识。
