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VEGF-induced choroidal damage in a murine model of retinal neovascularisation
  1. L B G Tee1,2,
  2. M A Penrose1,
  3. J E O’Shea1,
  4. C-M Lai3,
  5. E P Rakoczy3,
  6. S A Dunlop4
  1. 1
    School of Animal Biology, The University of Western Australia, Perth, Australia
  2. 2
    School of Medicine and Pharmacology, Curtin University of Technology, Perth, Australia
  3. 3
    Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia
  4. 4
    School of Animal Biology, Western Australian Institute for Medical Research, The University of Western Australia, Crawley, Australia
  1. Professor S A Dunlop, School of Animal Biology, Hackett Entrance No. 3 (M317), The University of Western Australia, Perth 6009, Australia; sarah{at}cyllene.uwa.edu.au

Abstract

Background/aims: Photoreceptor-specific upregulation of vascular endothelial growth factor (VEGF) in a transgenic mouse model (Kimba) of retinal neovascularisation induces retinal vascular damage which appears similar to that in diabetic retinopathy. Here we have determined whether the choroidal vasculature is also affected in Kimba.

Methods: Kimba mice were assessed with fundus fluorescein angiography for mild, moderate or severe retinal vascular leakage prior to preparation of choroidal corrosion casts for quantitative analysis using scanning electron microscopy. VEGF was located immunohistochemically.

Results: Choroidal abnormalities included microaneurysms, constriction, shrinkage and dropout in the capillaries and tortuosity and loops in the arteries and veins which were similar to those observed in corrosion casts of the human choroid in diabetes. Similar to human diabetes, choroidal neovascularisation was not observed. The severity of choroidal damage correlated with the extent of retinal vascular leakage. In addition to the expected presence of VEGF in photoreceptors, VEGF was also detected in the pigment epithelium and choroid in the transgenic mice.

Conclusion: We show that elevated retinal VEGF levels trigger pathophysiological changes in the choroid. We suggest that therapies to prevent vascular damage in diabetes must target both the retinal and choroidal vasculatures.

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Footnotes

  • Funding: JDRF and NH&MRC Program Grant and WestPac grant-in-aid. SAD is an NH&MRC Senior Research Fellow (Grant ID: 254670).

  • Competing interests: None.

  • Ethics approval: The work was approved by the Institutional Animal Ethics Committee.

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