Abstract
We have previously shown that sympathetic denervation results in significant blood
vessel growth of the choroid and retina. The mechanism of this growth remains unclear.
Since sympathetic denervation can result in increased nerve growth factor (NGF) levels,
it was the goal of this study to determine if choroidal and retinal endothelial cells
in culture would respond to nerve growth factor and if nerve growth factor promote
endothelial cell migration and proliferation, two components of angiogenesis. Western
blotting with phospho-specific antibodies, cell migration, and cell proliferation
assays were employed to determine NGF effects on both choroidal and retinal cell growth.
NGF treatment produced phosphorylation of TrkA in choroidal and retinal endothelial
cells. NGF stimulation resulted in activation of ERK1/2, Akt, and Src in choroidal
endothelial cells, while little phosphorylation was noted following NGF treatment
in retinal endothelial cells. NGF increased choroidal endothelial cell migration by
50% over control and this was inhibited by pretreatment with LY294002 (PI3K inhibitor),
Akt inhibitor, and MMP2/9 inhibitor. KT5823, PD98059, and PP2 did not affect choroidal
cell migration. NGF also produced a 47% increase in choroidal endothelial cell proliferation,
which was blocked by PP2, LY294002, Akt inhibitor, KT5823, and PD98059. NGF stimulation
did not alter retinal endothelial cell migration or proliferation. Thus, it appears
that increased NGF levels that may be noted after sympathectomy are capable of producing
some aspects of vascular remodeling via different signaling cascades in choroidal
endothelial cells in culture.
Keywords
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Article info
Publication history
Accepted:
July 1,
2003
Received in revised form:
June 28,
2003
Received:
May 20,
2003
Identification
Copyright
© 2003 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
