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Updated: Jul 6, 2026
An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
Published on: January 25, 2019
Unveiling the molecular complexity of proliferative diabetic retinopathy through scRNA-seq, AlphaFold 2, and machine
Jun Wang1, Hongyan Sun2, Lisha Mou3,4
1Department of Endocrinology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
Background:
Proliferative diabetic retinopathy (PDR), a major cause of blindness, is characterized by complex pathogenesis. This study integrates single-cell RNA sequencing (scRNA-seq), Non-negative Matrix Factorization (NMF), machine learning, and AlphaFold 2 methods to explore the molecular level of PDR.
Methods:
We analyzed scRNA-seq data from PDR patients and healthy controls to identify distinct cellular subtypes and gene expression patterns. NMF was used to define specific transcriptional programs in PDR. The oxidative stress-related genes (ORGs) identified within Meta-Program 1 were utilized to construct a predictive model using twelve machine learning algorithms. Furthermore, we employed AlphaFold 2 for the prediction of protein structures, complementing this with molecular docking to validate the structural foundation of potential therapeutic targets. We also analyzed protein-protein interaction (PPI) networks and the interplay among key ORGs.
Results:
Our scRNA-seq analysis revealed five major cell types and 14 subcell types in PDR patients, with significant differences in gene expression compared to those in controls. We identified three key meta-programs underscoring the role of microglia in the pathogenesis of PDR. Three critical ORGs (ALKBH1, PSIP1, and ATP13A2) were identified, with the best-performing predictive model demonstrating high accuracy (AUC of 0.989 in the training cohort and 0.833 in the validation cohort). Moreover, AlphaFold 2 predictions combined with molecular docking revealed that resveratrol has a strong affinity for ALKBH1, indicating its potential as a targeted therapeutic agent. PPI network analysis, revealed a complex network of interactions among the hub ORGs and other genes, suggesting a collective role in PDR pathogenesis.
Conclusion:
This study provides insights into the cellular and molecular aspects of PDR, identifying potential biomarkers and therapeutic targets using advanced technological approaches.
