Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor

Increased expression of vascular endothelial growth factor (VEGF) in the retina starting after postnatal day (P)7 results in neovascularization originating from deep retinal capillaries, but not those in the superficial capillary bed. Doxycycline was administered starting P0 to double transgenic mic...

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Bibliographic Details
Published in:Journal of cellular physiology 2004-06, Vol.199 (3), p.412-417
Main Authors: Oshima, Yuji, Deering, Tye, Oshima, Sachiko, Nambu, Hiroyuki, Reddy, P. Seshidhar, Kaleko, Michael, Connelly, Sheila, Hackett, Sean F., Campochiaro, Peter A.
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Angiopoietin-2 - pharmacology
Animals
Animals, Newborn
Anti-Bacterial Agents - pharmacology
Doxycycline - pharmacology
Genetic Vectors
Mice
Mice, Transgenic
Neovascularization, Physiologic
Retina - growth & development
Retinal Neovascularization
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Vascular Endothelial Growth Factor A - biosynthesis
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - pharmacology
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Summary:Increased expression of vascular endothelial growth factor (VEGF) in the retina starting after postnatal day (P)7 results in neovascularization originating from deep retinal capillaries, but not those in the superficial capillary bed. Doxycycline was administered starting P0 to double transgenic mice with inducible expression of VEGF in the retina. These mice showed proliferation and dilation of superficial retinal capillaries, indicating that at this stage of development, the superficial capillaries are sensitive to the effects of VEGF. Angiopoietin‐2 (Ang2) is expressed along the surface of the retina for several days after birth, but by P7 and later, Ang2 is only expressed in the region of the deep capillary bed. In mice with ubiquitous doxycycline‐inducible expression of Ang2, in the absence of doxycycline, intravitreous injection of a gutless adenoviral vector expressing VEGF (AGV.VEGF) resulted in neovascularization of the cornea and iris, but no retinal neovascularization. After treatment with doxycycline to induce Ang2 expression, intravitreous injection of AGV.VEGF caused retinal neovascularization in addition to corneal and iris neovascularization. The retinal neovascularization originated from both the superficial and deep capillary beds. These data suggest that Ang2 promotes sensitivity to the angiogenic effects of VEGF in retinal vessels. © 2004 Wiley‐Liss, Inc.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.10442