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Complement Depletion with Humanized Cobra Venom Factor in a Mouse Model of Age-Related Macular Degeneration

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Inflammation and Retinal Disease: Complement Biology and Pathology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 703))

Abstract

The effect of complement depletion with humanized cobra venom factor (CVF) on retinal lesion development/neovascularization was determined in a mouse model of wet age-related macular degeneration (AMD). Mice were treated with the humanized CVF protein HC3-1496 prior to, and once daily for 28 days after laser coagulation surgery of the retina. CVF transgenic mice exhibiting permanently low levels of serum complement activity and PBS-treated mice served as positive and negative controls, respectively. Fluorescein isothiocyanate (FITC)-dextran funduscopy after laser surgery indicated the presence of lesions in all mice that underwent laser surgery. In HC3-1496-treated mice as well as CVF transgenic mice smaller lesions were seen after 8 days. Measurement of lesion sizes by histopathological examination of eyes after 28 days revealed a significant reduction of lesion area and volume in both HC3-1496-treated animals and CVF transgenic animals compared to PBS-treated control animals. Systemic complement depletion with a complement depletor, such as the humanized CVF protein HC3-1496, represents a promising therapeutic concept for patients with wet AMD.

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Notes

  1. 1.

    Abbreviations: AMD age-related macular degeneration, CVF cobra venom factor, FITC fluorescein isothiocyanate, MAC membrane attack complex, RPE retinal pigmented epithelium.

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Acknowledgements

We thank Dr. Cynthia Cook for performing the laser surgery. Biostatistical support is gratefully acknowledged from the Biostatistical Shared Resource of the Cancer Research Center of Hawaii. This study was supported, in part, by Incode Biopharmaceutics, Inc., San Diego, CA.

Disclosure

D. Fritzinger, W. St. John, and C.-W. Vogel have a financial interest in Incode Biopharmaceutics, Inc., San Diego, CA.

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Authors and Affiliations

  1. Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, HI, 96813, USA

    David C. Fritzinger

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  1. David C. Fritzinger
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  2. Robin Dean
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  3. Carol Meschter
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  8. Carl-Wilhelm Vogel
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Corresponding author

Correspondence to David C. Fritzinger .

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Editors and Affiliations

  1. Department Of Pathology Laboratory Of, Medicine, University Of Pennsylvania, Johnson Pavilion 410, Philadelphia, 19104, USA

    John D. Lambris

  2. , Department of Ophthalmology and Visual S, University of Illinois at Chicago, Chicago, 62269-3745, USA

    Anthony P. Adamis

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Fritzinger, D.C. et al. (2010). Complement Depletion with Humanized Cobra Venom Factor in a Mouse Model of Age-Related Macular Degeneration. In: Lambris, J., Adamis, A. (eds) Inflammation and Retinal Disease: Complement Biology and Pathology. Advances in Experimental Medicine and Biology, vol 703. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5635-4_11

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