Cervical sympathectomy regulates expression of key angiogenic factors in the rat choroid.
Age-related macular degeneration is the leading cause of blindness in people over the age of 55. In addition to an increased risk of vision loss due to macular degeneration, aging results in a substantial loss of sympathetic nerve activity. We have previously shown that loss of sympathetic nerve activity to the eye causes significant remodeling of the choroidal vasculature. The hypothesis of the present study was that the choroidal remodeling noted after sympathectomy was due to alterations in key angiogenic growth factors. To test this hypothesis, female Sprague-Dawley rats underwent superior cervical ganglionectomy, which eliminates all sympathetic innervation to the eye. Six weeks after surgery, eyes were removed, and the choroidal tissue was processed for real-time PCR to measure gene expression and western blot analysis to assess protein expression. Gene and protein expression were significantly increased for vascular endothelial growth factor (VEGF) and pigment epithelial-derived growth factor (PEDF) in the sympathectomized eye, as compared to the contralateral eye (P < 0.05). Protein expression was increased 4-fold for angiopoietin1, with no change in steady-state gene expression. For both p53 and placental growth factor, steady-state mRNA levels were significantly decreased, while protein expression was significantly increased. Protein expression for Flt-1 was decreased significantly, with reduced gene expression. These results suggest that the vascular remodeling noted in the choroidal blood vessels after sympathectomy is a complex process involving numerous growth factor families. Therefore, modulation of sympathetic nerve activity may be a suitable mechanism to prevent the vascular growth associated with macular degeneration.
Steinle
Jena J
JJ
Department of Physiology, Southern Illinois University School of Medicine, 1135 Lincoln Drive, LSIII, Room 2071, Carbondale, IL, USA. jsteinle@siumed.edu
Lashbrook
Bethany L
BL
D043925:Angiogenesis Inducing Agents / Q000032:analysis*; D042683:Angiopoietin-1 / Q000032:analysis; D000818:Animals; D002829:Choroid / Q000737:chemistry; D005123:Eye / Q000294:innervation*; D005136:Eye Proteins / Q000032:analysis*; D005260:Female; D005728:Ganglia, Sympathetic / Q000601:surgery*; D015171:Ganglionectomy / Q000379:methods*; D005786:Gene Expression Regulation; D009414:Nerve Growth Factors / Q000032:analysis; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000032:analysis; D011480:Protease Inhibitors / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000032:analysis; D015843:Serpins / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D000099174:Pigment Epithelium-Derived Factor
D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D005136:Eye Proteins; D009414:Nerve Growth Factors; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D042787:Receptor, TIE-2; D015843:Serpins; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099174:Pigment Epithelium-Derived Factor; C000608038:Pgf protein, rat; C501164:Flt1 protein, rat