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

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 promo

SUBMITTER: He K 

PROVIDER: S-EPMC11929803 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature