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M Yan, KJ Baird, DT Cramb, WK StellNeuroscience Research Group Lions Sight Centre; Retinal and Choroidal Responses to Nitroprusside in the Chick: a Novel Animal Model for Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2736.
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Purpose: Age-related macular degeneration (AMD) is an important blinding condition, but understanding the pathogenetic mechanisms and developing effective therapies is impeded by the limited availability of good animal models. In chick eyes, sodium nitroprusside (SNP), a nitric oxide donor, damages photoreceptors and RPE at moderate supraphysiological doses (Gudgeon et al., 2002), suggesting an AMD-like condition. We are exploring whether choroidal neovascularization, associated with the "wet" form of AMD, occurs in this model. Methods: White Leghorn cockerels (N=16) were used. One eye was injected intravitreally with 100-200 nmol SNP in 20 µl saline (0.5-1.0 mM in vitreous), the other eye with saline only, and every other day x3 starting post-hatching day 8 (P8). On P13, chicks were sacrificed, the eyes removed and hemisected equatorially, eyecups fixed overnight in 4% buffered paraformaldehyde, viewed whole, cryosectioned and labeled immunocytochemically for vascular endothelial growth factor (VEGF-A, N-terminus). Results: SNP severely damaged RPE and photoreceptors, more in central than peripheral retina, often creating a circumscribed central disciform lesion. VEGF-like immunoreactivity (-IR) was at background levels in control eyes, but abundant in choroidal vascular endothelial cells in treated eyes. Choroidal whole mounts showed no neovascularization or other obvious vascular changes after such brief treatments. Conclusion: In the chick, moderate intravitreal doses of SNP are toxic to photoreceptors and RPE and acutely upregulate choroidal VEGF content. Further studies, using more prolonged treatment and survival times, will explore whether SNP also induces choroidal neovascularization. The SNP-treated chick eye may be a useful model for studying the mechanisms and treatment of AMD.
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