Nicotine promotes contribution of bone marrow-derived cells to experimental choroidal neovascularization in mice.
Nicotine can increase size and severity of experimental choroidal neovascularization (CNV); however, the mechanism is uncertain. Recent studies demonstrated that the development of CNV involves the contribution of bone marrow-derived cells (BMCs). This study aims to investigate the effects and the potential mechanism of nicotine on BMCs' contribution to CNV. Green fluorescent protein (GFP) chimeric mice were developed by transplanting bone marrow cells from GFP transgenic mice to C57BL/6J mice. CNV was induced by lasering. Nicotine was administered orally in drinking water. Histopathologic study and choroidal flatmount were performed to measure the CNV severity and BMCs recruitment. BMCs expressing different cell markers in CNV and local expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vascular cell adhesion molecule-1 (VCAM-1) were detected by immunofluorescence. Nicotine administration resulted in larger diameter and surface area of CNV (P<0.05). Nicotine-exposed mice demonstrated increased area and density of GFP+ cells, increased GFP+ vascular cells area, and decreased ratio of BMCs expressing F4/80 in CNV (P<0.05). Furthermore, the expression of VEGF and bFGF within CNV and VCAM-1 in choroid beneath CNV was up-regulated in nicotine-exposed mice. Our results suggest that nicotine promotes recruitment and incorporation of BMCs into CNV and affects differentiation of BMCs in CNV. These effects may be partly due to indirect actions of nicotine on BMCs via other factors (e.g. VEGF or VCAM-1). It is helpful to understand the mechanism of the effect of nicotine in CNV development.
Hou
Hui-Yuan
HY
Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Wang
Yu-Sheng
YS
Xu
Jian-Feng
JF
Wang
Bai-Ren
BR
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D017075:Laser Coagulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009538:Nicotine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D009538:Nicotine