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Single-Cell Transcriptomic Sequencing Reveals Tissue Architecture and Deciphers Pathological Reprogramming During
Lin Li1,2, Sipeng Zuo1,2, Yan Liu1,2
1Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Investigative Ophthalmology & Visual Science
|January 12, 2024
Summary
Acute retinal ischemia causes rod photoreceptor mitochondrial dysfunction and microglia activation. Targeting CXCL8 reduces inflammation and protects the retinal-blood barrier, offering insights into treating vision loss.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Acute retinal arterial ischemia diseases (ARAIDs) are critical emergencies requiring prompt treatment to prevent blindness.
- The molecular mechanisms driving ARAID pathogenesis are not fully understood.
Purpose of the Study:
- To investigate single-cell RNA sequencing (scRNA-seq) alterations in the primate retina during ischemia.
- To elucidate the molecular complexities underlying ARAIDs.
Main Methods:
- Established an ophthalmic artery occlusion model in Macaca fascicularis.
- Utilized scRNA-seq, bioinformatics, immunofluorescence, Western blot, and flow cytometry.
- Assessed microglia polarization status and transcriptional changes.
Main Results:
- Retinal ischemia impaired rod photoreceptor mitochondrial function, leading to rod cell loss.
- Ischemia induced significant transcriptional alterations in microglia activation.
- Targeting CXCL8 suppressed M1 microglia polarization and reduced inflammation in vitro.
- Endothelial cell apoptosis and increased microglia interaction were observed, impacting the retinal-blood barrier.
Conclusions:
- Identified pathological alterations in multiple retinal cell types during acute ischemia.
- Provided insights into ameliorating retinal damage and restoring vision.
