Abstract:Objective This study aimed to investigate the pathogenesis of Diabetic cataract (DC) by characterizing the morphological, cellular, and transcriptional changes in the lens of type 2 diabetes mellitus (T2DM) rats. Methods T2DM rat model was established via high-fat diet and streptozotocin injection. Slit-lamp was employed to inspect the lens of rats, and H E for evaluating histological alterations. Transcriptome sequencing was conducted on ocular anterior capsule to identify potential genes and validated by qRT-PCR. GO, KEGG and GSEA analyses were performed to investigate the predictive functions of differentially expressed genes (DEGs) and their associated biological pathways. Results Slit-lamp microscope revealed progressive opacification and vascular abnormalities in the anterior capsule of DM rats. H E staining showed disorganized cellular architecture and reduced density of lens epithelial cells (LECs). Transcriptome sequencing identified 1,691 DEGs between DM and NC rats, including 701 upregulated and 990 downregulated genes. Function enrichment analyses indicate the most changes happened to "visual perception," "photoreceptor outer segment," and "calcium ion binding" (GO terms), as well as "phototransduction, MAPK signaling", "PI3K-Akt signaling", and "cAMP signaling pathways" (KEGG). GSEA further demonstrated coordinated downregulation in visual signal-related pathways and upregulation in the apoptosis pathway in DM rats. qRT-PCR results of DEGs related to the above predictive functions analysis (Adgrv1, Cnga1, Cryga, Fgf9, Tlr4 and Casp12) from these pathways were consistant with transcriptome data. Conclusions This study identifies transcriptional reprogramming in the ocular anterior capsule of T2DM rats invloved in multiple pathways critical for visual function and lens homeostasis. These findings clarify diabetic cataract pathogenesis and provide potential biomarkers/targets for therapeutic intervention.