The Study
Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes
This study found that people who smoke tend to have worse eye damage from AMD, and in mice, it showed how smoking might make a specific protein cause trouble in eye blood vessels. But it didn’t prove smoking directly causes the damage — it just shows they often happen together.
Analysis score
Maximum 58 for a case-control study.
Where the score came from
Smoking makes a common blind-causing eye disease worse by sending immune cells that activate support cells in the eye, causing leaky blood vessels. Blocking a specific signal between these cells stops the damage.
Where does this study sit?
Reviews of RCTs (Meta-analyses)
Max 100Randomized Trials
Max 90Reviews of Cohort Studies
Max 85Cohort Studies
Max 72Reviews of Case-Control Studies
Max 63Case-Control Studies
Max 58Cross-Sectional & Case Series
Max 50Expert Opinion
Max 558 / 100
Quality score
Researchers compare people who have a condition (cases) with similar people who do not (controls), looking back in time for differences in exposure. Useful but more prone to bias.
Key takeaways
Summary
Based on the study abstract and findings.
- 1Yes — this means smokers get less benefit from current eye shots, but a new treatment targeting this pathway could help them see better when used together.
- 2Smokers had 2x higher retinal thickness after anti-VEGF treatment.
- 3In mice, blocking Sema4D reduced abnormal blood vessels as much as anti-VEGF, and combining both cut lesions in half more than either alone.
Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data
Publication
Journal
Nature Communications
Year
2025
Authors
Kai He, Xue Dong, Tianjing Yang, Ziqi Li, Yuming Liu, Jing He, Meng Wu, Selena Wei-Zhang, Parhat Kaysar, B. Cui, Xu Yao, Li Zhang, Wei Zhou, Heping Xu, Jun Wei, Qiang Liu, Junhao Hu, Xiaohong Wang, Hua Yan
Related Content
Claims (7)
People who smoke cigarettes have twice the risk of developing age-related macular degeneration due to oxidative damage and reduced blood flow to the retina.
People with neovascular age-related macular degeneration who smoke have thicker retinas and larger lesions after three anti-VEGF treatments than non-smokers with the same condition.
In mice, smoking raises Sema4D levels on certain immune cells, which bind to receptors on blood vessel support cells in the eye, causing those support cells to activate and destabilize blood vessels, resulting in larger abnormal blood vessel growth in the choroid.
Blocking Sema4D in mice with abnormal blood vessel growth in the eye reduces the size of the lesions and leakage from blood vessels as effectively as anti-VEGF treatment, and using both treatments together reduces them more than either treatment alone.
In cells of the eye called choroidal pericytes, the protein ROR2 is necessary for activating a signaling pathway involving PlexinB1 and RhoA that contributes to abnormal blood vessel growth in neovascular AMD.
In individuals with neovascular age-related macular degeneration and in mice exposed to smoke, choroidal pericytes show elevated levels of fibroblast and contractile proteins, which are associated with blood vessel instability and tissue scarring.
Not medical advice. For informational purposes only. Always consult a qualified healthcare professional before making health decisions.