晚期糖尿病视网膜病变小鼠视网膜功能衰退的系统评估与神经节细胞电生理异常特征OA

Objective To systematically depict the structural and functional panorama of the retina in advanced dia-betic retinopathy(DR)mouse models through multidimensional evaluation,with a focus on revealing the electrophysiologi-cal pathological characteristics of retinal ganglion cells(RGCs).Methods Streptozotocin was intraperitoneally injected to establish a DR mouse model.After the successful establishment of the DR model,the mice were randomly divided into a control group(CT group)and a DR group,with 12 mice in each group.At 15 weeks post-modeling,four mice from each group were randomly selected for optical coherence tomography to capture retinal images,for fundus fluorescein angiogra-phy to assess retinal vascular permeability,for optomotor response(OMR)testing to evaluate head tracking movement,and for electroretinography(ERG)to measure retinal electrophysiological characteristics.Subsequently,the mice were allocated for final sample collection according to a predefined protocol and using a randomization method:four mice per group were used for multi-electrode array(MEA)detection,four for real-time quantitative polymerase chain reaction(PCR),and four for retinal sectioning and histological/immunofluorescence analysis.The pancreatic and retinal tissues of the mice were sub-jected to hematoxylin-eosin staining for observation;the retinal microglial cells of the mice were subjected to immunofluo-rescence staining for observation;and real-time quantitative PCR was performed to measure the mRNA expression levels of various inflammation-related genes in the retina of mice.Results Staining of mouse tissue cells showed that,compared with the CT group,mice in the DR group exhibited retinal neuroinflammation,tissue structure damage,abnormal and region-specific expression profiles of inflammatory molecules in the retina and retinal pigment epithelium/choroidal microenviron-ment,increased Iba1 positive cell signaling in the retina,and severe vascular leakage and neovascularization.The OMR test results showed that the contrast sensitivity and spatial resolution of DR group mice were severely impaired.The ERG test re-sults showed that the cone cell pathway in DR group mice was severely damaged,and a severe functional decline of neurons in the inner layer of the retina occurred.The MEA test results showed that the self discharge of DR group mice RGCs was abnormally hyperactive and rhythmically disrupted,and their peak response frequency and information encoding ability in-duced by light stimulation were severely weakened.Conclusion The visual function impairment in DR mice is closely re-lated to the decrease in signal-to-noise ratio caused by the disruption of retinal network homeostasis.Protecting RGC func-tion and maintaining network homeostasis may have potential therapeutic value.