Inflammation-Mediated Immune Imbalance in the Pathogenesis of Diabetic Cataracts

Background: Diabetes increases the risk of cataract formation fivefold. Immune-mediated inflammation has been reported to play a role in this process; however, whether alterations in the immune landscape are involved remains unknown. Therefore, we conducted a multi-omics analysis to evaluate the impact of immune inflammation on the lens. Methods: Bulk RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from diabetic patients and lens tissues from diabetic rats. Single-cell RNA sequencing was utilized to characterize intercellular interactions. Key gene and protein expressions were validated via laboratory assays. Results: An integrated RNA-seq analysis revealed a disruption of the blood–aqueous barrier integrity in the diabetic group, enhanced monocyte migration and adhesion, increased differentiation from classical to non-classical monocytes, and the upregulation of TNF and IFN-γ signaling pathways. The transcriptomic profiling of rat lenses revealed an increased proportion of monocytes and the activation of apoptotic pathways in lens epithelial cells. Immunohistochemistry and immunofluorescence staining demonstrated elevated caspase-3 and IL-6 levels in lens epithelial cells and increased immune cell infiltration in the diabetic group. The qRT-PCR and ELISA confirmed elevated levels of the pro-inflammatory cytokines IL-6 and IFN-γ, alongside reduced anti-inflammatory cytokine IL-10 in the peripheral blood and aqueous humor of diabetic patients. Conclusions: Diabetes alters the peripheral immune microenvironment and disrupts the blood–aqueous barrier, promoting intraocular inflammation and lens epithelial cell apoptosis, thereby accelerating cataract development.