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Fluorescein angiography, optical coherence tomography, and histopathologic findings in a VEGF165 animal model of retinal angiogenesis

  • Retinal Disorders
  • Published:
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Abstract

Background

To establish an animal model of retinal neovascularization using vascular endothelial growth factor (VEGF165) and analyze the model using optical coherence tomography (OCT), fluorescein angiography (FA), and histopathologic evaluation.

Methods

Twelve rabbits were divided into groups as follows: group 1 (n = 3), sham intravitreous injections of 0.1 ml of balanced saline; group 2 (n = 6), one 10-μg intravitreal injection of VEGF165 on day 0; and group 3 (n = 3), two 10-μg intravitreal injections of VEGF165, one on day 0 and one on day 7. Follow-up evaluations (days 0, 3, 7, 14, 21, 28) included obtaining fundus color photographs and FA, OCT, and histopathologic examinations. Eyes were enucleated and stained with hematoxylin and eosin (H&E).

Results

One injection of VEGF (group 2) was associated with dilatation and tortuosity of the retinal blood vessels that developed within 72 h. Retinal neovascularization was present by day 7 and regressed by day 14. However, even on day 28, the capillaries were still tortuous. Two VEGF injections (group 3) caused increased leakage and neovascularization up to day 14; severe capillary nonperfusion was seen during week 4. At the end of the follow-up period, OCT and histopathologic examination of group 3 showed peripapillary tractional retinal detachments. By day 7, the differences between the retinal thickness seen on OCT in groups 2 and 3 and the group 1 control group were significant (p < 0.001). The histologic findings showed increased vessel size in groups 2 and 3 by days 14 and 28 compared with the controls.

Conclusions

FA, OCT, and histopathologic findings showed that this retinal neovascularization model is efficient, sustainable, and reliable. One injection of VEGF165 created neovascularization that peaked after 1 week; two injections created more intense neovascularization that evolved to retinal detachments after 4 weeks.

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Declaration of interest

The authors report no financial conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    Luís A. Arana, Anderson T. Pinto, Gerald J. Chader, Jose D. Barbosa, Sabina Morales & Mark S. Humayun

  2. Department of Ophthalmology, Federal University of Parana, Rua Padre Anchieta 1251, Curitiba, PR, Brazil

    Luís A. Arana & Ana T. Moreira

  3. Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, SP, Brazil

    Anderson T. Pinto & Mauricio Maia

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  1. Luís A. Arana
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  2. Anderson T. Pinto
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Correspondence to Luís A. Arana.

Additional information

This manuscript is part of Dr. Arana’s master thesis from the postgraduate program in clinical surgery of Federal University of Parana.

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Arana, L.A., Pinto, A.T., Chader, G.J. et al. Fluorescein angiography, optical coherence tomography, and histopathologic findings in a VEGF165 animal model of retinal angiogenesis. Graefes Arch Clin Exp Ophthalmol 250, 1421–1428 (2012). https://doi.org/10.1007/s00417-012-1978-8

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  • DOI: https://doi.org/10.1007/s00417-012-1978-8

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