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| Status |
Public on Jan 26, 2025 |
| Title |
Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Age-related macular degeneration (AMD) is a prevalent neuroinflammation condition and the leading cause of irreversible blindness among the elderly population. Smoking significantly increases AMD risk, yet the mechanisms remain unclear. Here, we investigated the role of Sema4D-PlexinB1 axis in the progression of AMD, in which Sema4D-PlexinB1 is highly activated by smoking. Using patient-derived samples and mouse models, we discovered that smoking increased the presence of Sema4D on the surface of CD8+ T cells that migrated into the choroidal neovascularization (CNV) lesion via CXCL12-CXCR4 axis and interacted with its receptor PlexinB1 on choroidal pericytes. This led to ROR2-mediated PlexinB1 phosphorylation and pericytes activation, hence disrupted vascular homeostasis and promoted neovascularization. Inhibition of Sema4D reduced CNV and improved the benefit of anti-VEGF treatment. In conclusion, this study unveils the molecular mechanisms through which smoking exacerbates AMD pathology, and presents a potential therapeutic strategy by targeting Sema4D to augment current AMD treatments.
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| Overall design |
To investigate the effects of smoking on neovascular age-related macular degeneration (nvAMD) in mice, we performed single cell transcriptome sequencing on the retinal-choroid complex of C57BL/6J mice. The mice were exposed to cigarette smoke, with or without laser-induced choroidal neovascularization (CNV) modeling. Transcriptome sequencing was conducted on the retinal-choroid complex three days after modeling, with four groups: Smoke group and Smoke+CNV group.
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| Contributor(s) |
He K, Dong X, Yang T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jan 25, 2025 |
| Last update date |
Jan 27, 2025 |
| Contact name |
钰云 王 |
| E-mail(s) |
hekai24@126.COM
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| Phone |
17320271719
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| Organization name |
天津医科大学
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| Street address |
Tianjin
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| City |
Tianjin |
| ZIP/Postal code |
300000 |
| Country |
China |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1215754 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE288036_expr_matrix.csv.gz |
1.0 Gb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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