Abstract
Age-related macular degeneration remains to be a major cause of irreversible blindness in the world. In this disease, neovascularization plays an important role in disease burden and progression. Current therapies focus on inhibition of neovascularization through suppression of the extracellular VEGF pathway. However, these strategies have several disadvantages including the need for monthly injections and the need for direct injections of drug therapies to the eye. Moreover, none of these strategies currently focus on inhibition of intracellular VEGF signaling. Here, we describe our recent efforts at developing (I) a novel VEGF inhibition strategy that utilizes Flt-1 intracellularly to suppress VEGF before being secreted out of the cell. We also describe our novel strategy of (II) delivering Flt-1 to sites of neovascularization in the eye using a nonviral, intravitreal-injection-free approach, utilizing surface-functionalized nanoparticles. Using this strategy, we are able to suppress choroidal neovascularization and fibrosis and restore visual acuity in several animal models including nonhuman primates. Our results show a promising alternative in our arsenal for anti-VEGF therapies.
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Conflict of Interest
Author Balamurali K. Ambati declares that he has issued a patent on the technologies discussed in the chapter.
Author Samuel F. Passi declares that he has no conflict of interest.
Author Cecinio C. Ronquillo declares that he has no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
Animal Studies
All institutional and national guidelines for the care and use of laboratory animals were followed. All experiments were approved by the IACUCs of Medical College of Georgia, University of Colorado Denver, and University of Utah for the experiments performed at the respective sites.
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Ronquillo, C.C., Passi, S.F., Ambati, B.K. (2015). Restoring Physiologic Barriers Against Neovascular Invasion. In: Rakoczy, E. (eds) Gene- and Cell-Based Treatment Strategies for the Eye. Essentials in Ophthalmology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45188-5_8
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DOI: https://doi.org/10.1007/978-3-662-45188-5_8
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