Fig. 9: Working model.

A schematic illustration presents the mechanisms. Smoking increases the expression of Sema4d in peripheral CD8+ T cells, which are then recruited to the CNV lesion area via the CXCL12-CXCR4 axis. These T cells act on PlexinB1 of pericytes, activating them and thereby exacerbating CNV damage. Meanwhile, ROR2 on pericytes is a co-activating receptor for Sema4D-mediated PlexinB1 activation, promoting the phosphorylation of PlexinB1 and the activation of RhoA, which subsequently regulates pericyte proliferation, migration, and contraction.