Single-Cell Transcriptomics Reveals a Multi-Compartmental Cellular Cascade Underlying Elahere-Induced Ocular Toxicity in Rats
Abstract
1. Introduction
2. Results
2.1. Elahere Administration Induces Clinically and Histologically Evident Ocular Toxicity in Rats
2.2. Single-Cell Transcriptomic Profiling Reveals Cellular Changes in the Cornea After Elahere Treatment
2.3. Elahere Induces Immune Cell Depletion and Reprogramming, Especially in Macrophages
2.4. Elahere Disrupts Corneal Epithelial Differentiation and Promotes Progenitor Accumulation
2.5. Elahere Triggers Endothelial Cell Injury and Pro-Fibrotic Stromal Remodeling
2.6. Elahere Treatment Remodels Intercellular Communication Networks in the Cornea
3. Discussion
4. Materials and Methods
4.1. Animal Model and Elahere Administration
4.2. Ocular Toxicity Assessment
4.3. Corneal Tissue Processing and Single-Cell Sequencing
4.4. Single-Cell RNA-Seq Data Processing
4.5. Differential Gene Expression Analysis
4.6. Pathway Enrichment Analysis
4.7. Pseudotime Trajectory Analysis
4.8. Cell–Cell Interaction Analysis
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ADCs | Antibody-Drug Conjugates |
ADCC | Antibody-Dependent Cellular Cytotoxicity |
ADCP | Antibody-Dependent Cellular Phagocytosis |
DEGs | Differential Expressed Genes |
ECM | extracellular matrix |
FcγR | Fc gamma receptor |
FRα/Folr1 | folate receptor α |
GEO | Gene Expression Omnibus |
H&E | Hematoxylin and Eosin |
IACUC | Institutional Animal Care and Use Committee |
LSC | limbal stem cell |
MHC | Major Histocompatibility Complex |
NK | natural killer |
PCA | Principal Component Analysis |
scRNA-seq | single-cell RNA sequencing |
TGFβ | Transforming Growth Factor Beta |
UMAP | Uniform Manifold Approximation and Projection |
UMIs | unique molecular identifiers |
VEGF | Vascular Endothelial Growth Factor |
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Zhang, J.; Li, M.; Yang, Y.; Guo, P.; Li, W.; An, H.; Cui, Y.; Guo, L.; Duan, M.; Lu, Y.; et al. Single-Cell Transcriptomics Reveals a Multi-Compartmental Cellular Cascade Underlying Elahere-Induced Ocular Toxicity in Rats. Pharmaceuticals 2025, 18, 1492. https://doi.org/10.3390/ph18101492
Zhang J, Li M, Yang Y, Guo P, Li W, An H, Cui Y, Guo L, Duan M, Lu Y, et al. Single-Cell Transcriptomics Reveals a Multi-Compartmental Cellular Cascade Underlying Elahere-Induced Ocular Toxicity in Rats. Pharmaceuticals. 2025; 18(10):1492. https://doi.org/10.3390/ph18101492
Chicago/Turabian StyleZhang, Jialing, Meng Li, Yuxuan Yang, Peng Guo, Weiyu Li, Hongxin An, Yongfei Cui, Luyun Guo, Maoqin Duan, Ye Lu, and et al. 2025. "Single-Cell Transcriptomics Reveals a Multi-Compartmental Cellular Cascade Underlying Elahere-Induced Ocular Toxicity in Rats" Pharmaceuticals 18, no. 10: 1492. https://doi.org/10.3390/ph18101492
APA StyleZhang, J., Li, M., Yang, Y., Guo, P., Li, W., An, H., Cui, Y., Guo, L., Duan, M., Lu, Y., Yu, C., & Wang, L. (2025). Single-Cell Transcriptomics Reveals a Multi-Compartmental Cellular Cascade Underlying Elahere-Induced Ocular Toxicity in Rats. Pharmaceuticals, 18(10), 1492. https://doi.org/10.3390/ph18101492