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Nicotine stimulates retinal angiogenesis via α7‐nicotinic receptor and matrix metalloproteinases (MMP)‐mediated signaling pathway
Author(s) -
Buckley Adam W.,
Brown Kathleen C.,
Dom Aaron M.,
Weller Donald W.,
Shah Yashoni H.,
Egleton Richard D.,
Dasgupta Piyali
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.750.6
Subject(s) - angiogenesis , retinal , macular degeneration , retina , medicine , nicotinic agonist , nicotine , matrix metalloproteinase , pharmacology , microbiology and biotechnology , endocrinology , biology , ophthalmology , receptor , neuroscience
Proliferative retinopathies are among the leading causes of blindness in the elderly. These diseases are characterized by aberrant retinal angiogenesis, which leads to compromised function of the retina and ultimately loss of vision. Smoking is one of the major risk factors for the development of proliferative retinopathies, such as age related macular degeneration (ARMD) and diabetic retinopathy. Our study examined whether nicotine stimulates retinal angiogenesis if administered at concentrations commonly found in the plasma of smokers. Results indicated that treatment with nicotine enhanced angiogenic‐tubule formation in Matrigel duplex assays using primary human retinal microvascular endothelial cells. Nicotine also induced sprouting angiogenesis in retinal explants isolated from Zucker rats. The proangiogenic effects of nicotine were mediated by α7 nicotinic acetylcholine receptors (nAChRs) and downstream activation of MMP‐2 and MMP‐9. Most importantly, antagonists of α7‐nAChRs potently inhibit nicotine‐induced retinal angiogenesis in both duplex assays and rat retinal explants. Our results suggest that α7‐nAChR may be a valuable molecular target for therapy of ARMD. Funding for our study was supported by the American Retina Foundation, the INBRE Summer Program, the Sigma Xi GIAR, an MU‐ADVANCE Fellowship, and the Flight Attendant Medical Research Institute YCSA Grant.