An Exploratory Single-Cell Analysis Identifies Candidate Shared Molecular Features in Proliferative Diabetic Retinopathy and Parkinson’s Disease

Background: Diabetic retinopathy (DR) and Parkinson’s disease (PD) are prevalent, progressive disorders that cause irreversible visual impairment and motor dysfunction, respectively. Increasing evidence suggests that retinal alterations may precede and predict neurodegeneration in PD, indicating potential shared pathogenic mechanisms. This study aimed to delineate the molecular and cellular connections between DR and PD, with a particular focus on their convergent neuroimmune and vascular pathways. Methods: We integrated single-cell RNA sequencing (scRNA-seq) datasets derived from proliferative DR (PDR) retinal fibrovascular membranes and PD brain tissues. Cell-type-associated transcriptional features were identified within each dataset, and corresponding cell populations were compared to identify candidate overlapping molecular features. CellChat was used to infer potential ligand–receptor interactions between cell populations. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore associated biological pathways and transcriptional programs. Results: A2M, NRP1, and ETS2 were identified as candidate shared transcriptional features in corresponding microglial and endothelial cell populations across the PDR and PD datasets. CellChat analysis predicted an ITGB2–ICAM1 (integrin beta-2-Intercellular Adhesion Molecule 1) ligand–receptor interaction in both datasets, although the predicted sender–receiver relationships differed according to tissue context. GSEA and GSVA identified overlapping inflammatory, apoptotic, hypoxia-related, and epithelial–mesenchymal transition-associated transcriptional programs across the analyzed datasets. These findings suggest potentially convergent immune–vascular and inflammatory features between PDR and PD. Conclusions: This exploratory single-cell analysis identified candidate cell-type-associated transcriptional features and potential cell–cell communication patterns shared between PDR and PD. The predicted ITGB2–ICAM1 interaction provides a hypothesis for further investigation of immune–vascular communication.