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2013 - CTS 2013 Congress


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Oral Communications 9

20.2 - Setting-up of a chimeric animal model to verify the role of bone marrow-derived endothelial progenitor cells in the development of age-related macular degeneration (AMD)

Presenter: Silvia, Maestroni, Milan, Italy
Authors: Silvia Maestroni1, Anna Maestroni1, Mandelli Giacomo1, Giuliana Ferrari1, Ilaria Zucchiatti1, Rosangela Lattanzio1, Gemma Tremolada1, Simona Ceglia1, Francesco Bandello1, Gianpaolo Zerbini1

Setting-up of a chimeric animal model to verify the role of bone marrow-derived endothelial progenitor cells in the development of age-related macular degeneration (AMD).

Silvia Maestroni1, Anna Maestroni1, Mandelli Giacomo1, Giuliana Ferrari1, Ilaria Zucchiatti1, Rosangela Lattanzio1, Gemma Tremolada1, Simona Ceglia1, Francesco Bandello1, Gianpaolo Zerbini1

1Ospedale San Raffaele s.r.l., Milan, Italy

 

Age-related macular degeneration (AMD) is a debilitating disease that causes vision loss and represents the leading cause of blindness in industrialized countries among adults older than 60 years. Most cases of severe vision loss in AMD result from the development of choroidal neovascularization (CNV), which occurs in approximately 10% of patients with AMD. The abnormal new blood vessels grow from the choroidal capillaries through Bruch’s membrane and into the spaces beneath the retinal pigment epithelium and the retina.
The mechanisms that cause CNV are still unclear, but it is known that once the process is triggered, the lesion grows rapidly. In humans, the therapeutic benefit of intravitreal injections of agents that target vascular endothelial growth factor (VEGF) indicates that angiogenesis (the process that involves the migration, proliferation, and remodeling of endothelial cells derived from preexisting vessels) is one of the processes that sustain the rapid formation of the new capillaries in CNV. A parallel role of endothelial progenitor cells (EPCs) recruited to the process from bone marrow (so called vasculogenesis) cannot however be presently ruled out.
To verify this issue, bone marrow transplantation was performed in 20 C57BL mice using a GFP transgenic strain as a donor and a co-isogenic strain as the recipient. Choroidal neovascolarization was then induced by laser treatment aimed to obtain a major retinal damage (disrupture of Bruch's membrane), a procedure that gave rise to choroidal neovascularization approximately 15 days after treatment.
Choroidal neovascularization was confirmed in vivo by simultaneous Fluorescein Angiography and Optical Coherence Tomography (OCT)  (Spectralis™ device from Heidelberg Engineering).  After this procedure, the animals were perfused with TRITC-labeled dextrans to highlight retinal vascularization and sacrificed. The eyes were then removed, the retina extracted and treated appropriately to obtain retinal whole-mounts. Under fluorescence the perfused retinal vascular tree could be evaluated and EPCs were detectable along the vessels being GFP+. Staining to confirm EPCs phenotype was performed and quantification of EPCs involvement in neovascularization was performed by analysis of digital pictures. Altogether our results confirmed this chimeric mouse as a valid model of AMD of potential use to test the effect of novel drugs on the onset and progression of this sight-threatening disease.


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