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Increased expression of VEGF in retinal pigmented epithelial cells is not sufficient to cause choroidal neovascularization
Author(s) -
Oshima Yuji,
Oshima Sachiko,
Nambu Hiroyuki,
Kachi Shu,
Hackett Sean F.,
Melia Michele,
Kaleko Michael,
Connelly Sheila,
Esumi Noriko,
Zack Donald J.,
Campochiaro Peter A.
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20110
Subject(s) - retina , choroidal neovascularization , retinal , biology , neovascularization , vascular endothelial growth factor , retinal pigment epithelium , vascular endothelial growth factor a , kinase insert domain receptor , macular degeneration , microbiology and biotechnology , ophthalmology , cancer research , angiogenesis , medicine , vegf receptors , neuroscience , biochemistry
Increased expression of vascular endothelial cell growth factor (VEGF) in the retina is sufficient to stimulate sprouting of neovascularization from the deep capillary bed of the retina, but not the superficial retinal capillaries or the choriocapillaris. Coexpression of VEGF and angiopoietin 2 (Ang2) results in sprouting of neovascularization from superficial and deep retinal capillaries, but not the choriocapillaris. However, retina‐derived VEGF and Ang2 may not reach the choriocapillaris, because of tight junctions between retinal pigmented epithelial (RPE) cells. To eliminate this possible confounding factor, we used the human vitelliform macular dystrophy 2 (VMD2) promoter, an RPE‐specific promoter, combined with the tetracycline‐inducible promoter system, to generate double transgenic mice with inducible expression of VEGF in RPE cells. Adult mice with increased expression of VEGF in RPE cells had normal retinas and choroids with no choroidal neovascularization (CNV), but when increased expression of VEGF in RPE cells was combined with subretinal injection of a gutless adenoviral vector containing an expression construct for Ang2 (AGVAng2), CNV consistently occurred. In contrast, triple transgenic mice with induced expression of Ang2 and VEGF in RPE cells, did not develop CNV. These data suggest that increased expression of VEGF and/or Ang2 in RPE cells is not sufficient to cause CNV unless it is combined with a subretinal injection of a gutless adenoviral vector, which is likely to perturb RPE cells. These data also suggest that the effects of angiogenic proteins may vary among vascular beds, even those that are closely related, and, therefore, generalizations should be avoided. © 2004 Wiley‐Liss, Inc.