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Sensitivity of Different Vascular Beds in the Eye to Neovascularization and Blood-Retinal Barrier Breakdown in VEGF Transgenic Mice

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Angiogenesis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 476))

Abstract

Neovascularization (NV) causes visual deficits in ocular disorders such as diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. An understanding of the angiogenic factors promoting this abnormal vascular growth is necessary to devise a therapeutic approach to inhibit NV. One factor known to promote NV is vascular endothelial growth factor (VEGF), which can also induce a breakdown of the blood-retinal barrier (BRB) leading to macular edema, another major cause of visual loss in a variety of ocular disorders. To investigate the role of VEGF on ocular NV, transgenic mice have been produced that overexpress VEGF in the photoreceptors under control of the rhodopsin promoter. Eyes from these mice and from littermates not expressing the transgene were examined using immunohistochemistry, griffonia simplicifolia isolectin-B4 (GSA) staining to clearly visualize vessels, and electron microscopy. Levels of transgene expression were determined by the polymerase chain reaction. In normal mice, retinal vessels are organized into a superficial and a deep capillary bed with some vessels forming a shunt between both beds. In a transgenic line of mice that overexpresses VEGF (V-6), NV originates from the deep capillary bed at about postnatal day 10 (P10) and extends through the photoreceptor layer to form vascular complexes in the subretinal space with BRB breakdown occurring only in the area of NV. The superficial capillary bed and the choroidal vasculature are unaffected. In another line of transgenic mice with a higher expression rate of VEGF (V-24), photoreceptor degeneration begins at P7-8, soon after the onset of transgene expression, without widespread NV, as was observed in V-6 mice. In conclusion, overexpression of VEGF in transgenic mice is sufficient to cause retinal NV, but only the deep capillary bed is responsive. Increasing the expression of VEGF does not necessarily increase the amount of NV. A better understanding of the specific factors and conditions that result in a particular pattern of ocular NV may provide clues regarding the pathogenesis of ocular neovascular disease.

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Authors and Affiliations

  1. The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 825 Maumenee Bldg., 600 N. Wolfe St., Baltimore, MD, 21287-9289, USA

    S. A. Vinores, N. L. Derevjanik, M. A. Vinores, N. Okamoto & P. A. Campochiaro

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  1. S. A. Vinores
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  2. N. L. Derevjanik
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  3. M. A. Vinores
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  4. N. Okamoto
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  5. P. A. Campochiaro
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  1. University of Patras Medical School, Patras, Greece

    Michael E. Maragoudakis

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Vinores, S.A., Derevjanik, N.L., Vinores, M.A., Okamoto, N., Campochiaro, P.A. (2000). Sensitivity of Different Vascular Beds in the Eye to Neovascularization and Blood-Retinal Barrier Breakdown in VEGF Transgenic Mice. In: Maragoudakis, M.E. (eds) Angiogenesis. Advances in Experimental Medicine and Biology, vol 476. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4221-6_11

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  • DOI: https://doi.org/10.1007/978-1-4615-4221-6_11

  • Publisher Name: Springer, Boston, MA

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