大鼠糖尿病性白内障相关的关键通路及基因OA

Objective This study aimed to investigate the pathogenesis of diabetic cataract(DC)by characterizing morphological,cellular,and transcriptional changes in the anterior lens capsule in rats with type 2 diabetes mellitus(T2DM).Methods A T2DM rat model was established using a high-fat,high-sugar diet and intraperitoneal injection of streptozotocin.Eye lenses were examined by slit-lamp microscopy and histological alterations were evaluated by hematoxylin-eosin(HE)staining.Transcriptome sequencing of the lens capsule was carried out to identify differentially expressed genes(DEGs)and validated by real-time quantitative polymerase chain reaction(qPCR).Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analyses(GSEA)were performed to investigate the predictive functions of DEGs and their associated biological pathways.Results Slit-lamp microscopy revealed progressive opacification in the lens in T2DM rats.HE staining showed disorganized cellular architecture and reduced density of lens epithelial cells(P＜0.01).Transcriptome sequencing identified 1 601 DEGs between T2DM and control rats,including 701 upregulated and 900 downregulated genes.Functional enrichment analyses indicated that most changes occurred in"visual perception""photoreceptor outer segment"and"Ca2+binding"(GO enrichment),as well as"phototransduction""MAPK signaling""PI3K-Akt signaling"and"cAMP signaling pathways"(KEGG enrichment).GSEA further demonstrated coordinated downregulation in visual signal-related pathways and upregulation in the apoptosis pathway in DM rats.The qPCR results of DEGs related to the above predictive functions analysis(Adgrv1,Cnga1,Cryga,Fgf9,Tlr4,and Casp12)from these pathways were consistent with transcriptome data.Conclusions This study identified transcriptional reprogramming in the anterior lens capsule of T2DM rats involved in multiple pathways critical for visual function and lens homeostasis.These findings clarify the pathogenesis of DC and provide potential biomarkers/targets for therapeutic intervention.