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Y. Oshima, S. Oshima, K. Takahashi, H. Nambu, R.S. Apte, E. Duh, S.F. Hackett, D.J. Zack, P.A. Campochiaro; Angiopoietin 2 (Ang2) Increases or Decreases Neovascularization (NV) Depending Upon the Setting . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4519.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the role of ang2 in the retina. Methods: Five independent lines of tetracycline response element (TRE)/murine ang2 (TRE/ang2) transgenic mice were generated. These mice were crossed with reverse tetracycline transactivator (rtTA)/rhodopsin promoter (rtTA/rho) or rtTA/CMV promoter (rtTA/CMV) mice to generate double transgenics. Expression of ang2 was evaluated by RT-PCR and immunohistochemistry. Mice with doxycycline (dox)-inducible ubiquitous expression of ang2 (rtTA/CMV-TRE/ang2) or dox-inducible expression of ang2 in the retina (rtTA/rho-TRE/ang2) were used to investigate the effect of increased expression of ang2 on retinal vascular development, ischemic retinopathy, VEGF-induced subretinal NV, and choroidal NV (CNV). Results: Mothers of newborn rtTA/CMV-TRE/ang2 mice were given drinking water supplemented with doxycycline (dox) and pups were given subcutaneous injections of dox from P8-P10. At P11, compared to untreated double transgenics, dox-treated mice showed increased expression of ang2 in the retina and accelerated development of the deep capillary bed. Although this physiologic angiogenesis was accelerated, it did not overshoot and by P18 the difference between dox-treated and untreated mice disappeared. Compared to untreated rtTA/CMV-TRE/ang2 mice with oxygen-induced ischemic retinopathy, those treated with dox had significantly more retinal NV. Adult rtTA/rho-TRE/ang2 mice that also carried a rho/VEGF transgene had subretinal NV typical of rho/VEGF mice when untreated, but the NV regressed when ang2 expression was induced by dox treatment. Likewise, when adult rtTA/rho-TRE/ang2 mice with CNV at Bruch’s membrane rupture sites were treated with dox, the CNV regressed. Conclusions: Increased expression of ang2 in hypoxic retina enhances retinal NV, but in normoxic eyes ang2 causes regression of subretinal or choroidal NV.
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