Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes

Kai He, Xue Dong, Tianjing Yang, Ziqi Li, Yuming Liu, Jing He, Meng Wu, Selena Wei-Zhang, Parhat Kaysar, Bohao Cui, Xueming Yao, Li Zhang, Wei Zhou, Heping Xu, Jun Wei, Qiang Liu, Junhao Hu (), Xiaohong Wang () and Hua Yan ()
Additional contact information
Kai He: Tianjin Medical University General Hospital
Xue Dong: Tianjin Medical University General Hospital
Tianjing Yang: Nankai University
Ziqi Li: Tianjin Medical University General Hospital
Yuming Liu: Tianjin Medical University General Hospital
Jing He: Chinese Academy of Sciences
Meng Wu: Tianjin Medical University General Hospital
Selena Wei-Zhang: Tianjin Medical University General Hospital
Parhat Kaysar: Tianjin Medical University General Hospital
Bohao Cui: Tianjin Medical University General Hospital
Xueming Yao: Nankai University
Li Zhang: The Second Affiliated Hospital of Chongqing Medical University
Wei Zhou: Tianjin Medical University General Hospital
Heping Xu: Queen’s University Belfast
Jun Wei: Chinese Academy of Medical Sciences & Peking Union Medical College
Qiang Liu: Tianjin Medical University General Hospital
Junhao Hu: Chinese Academy of Sciences
Xiaohong Wang: Tianjin Medical University General Hospital
Hua Yan: Tianjin Medical University General Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-25

Abstract: Abstract 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 investigate 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 discover that smoking increases the presence of Sema4D on the surface of CD8+ T cells that migrate into the choroidal neovascularization (CNV) lesion via CXCL12-CXCR4 axis and interact with its receptor PlexinB1 on choroidal pericytes. This leads to ROR2-mediated PlexinB1 phosphorylation and pericyte activation, thereby disrupting vascular homeostasis and promoting neovascularization. Inhibition of Sema4D reduces CNV and improves 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58074-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58074-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58074-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().