Abstract
The eye is rich in oxidizable substrates which often increase in ocular disease. In vivo rabbit models described in this chapter provide valuable clinical and biomolecular data, whereas in vitro models are used to define physiological observations such as endothelial cell proliferation, migration and vascular tube formation. Antioxidant supplementation significantly inhibits these phenomena and is facilitated when multiple antioxidants are given simultaneously. The 13-isomer of linoleic acid hydroperoxide (HpODE) stimulates neovascularization when injected into the corneal stroma, the vitreous, or subretinal to create appropriate animal models. During this process, nuclear factors, metalloproteinase and angiogenic cytokines are upregulated within 3–6 h to initiate the neovascular response. Fluorescein angiography provides direct visualization of new vessel growth. A variety of oxidative stress biomarkers can be measured in plasma, ocular homogenates and tissue culture cells, or media. Histology confirms location of injected HpODE, presence or absence of an inflammatory response, hemorrhage and illustrate features that resemble human disease. New vessels grow at the rate of 0.3 mm/day and plateau at 3–4 weeks as the HpODE stimulus is metabolized. Repeat injections result in an accelerated growth rate. Vessel length in diabetic rabbits is double that observed in normal animals. In contrast to surgical or laser-induced neovascularization models, the HpODE model uses a natural substrate and is considered a non-traumatic procedure. All models are valuable to validate antioxidant intervention studies in clinical trials.
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Acknowledgements
The authors thank the following scientists who assisted in these various studies: Akira Higa, Shohei Fukuda, Eichi Nishimura, Richard Browne, Ahmad Aljada, Kathleen Dorey, Ram Sasisekharan, Tadahisa Hiramitsu, Shigehiro Iwabushi, Yuichiro Ogura, Alihisa Matsubara, Mary E. Hartnett, Kaori Watanabe, Miho Chida, Maki Kamegawa, Richard Spaide, Wang Ho-Spaide, Maria Grant and E. Ann Ellis. We also thank Professors Ryohei Koide and Hajimi Yasuhara for department and institutional support and technical assistance and Oxidative Stress Associates for administrative financial aid.
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Ueda, T., Nakanishi, T., Tamai, K., Iwai, S., Armstrong, D. (2011). Neovascular Models of the Rabbit Eye Induced By Hydroperoxide. In: Basu, S., Wiklund, L. (eds) Studies on Experimental Models. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-956-7_14
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