Vitreous protein binding with nanopore dialysis membrane device
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Vitreous protein binding with nanopore dialysis membrane device Jeffrey L. Olson 1 & Raul Velez-Montoya 1 & Anna Mackin 1 & Niranjan Manoharan 1 & Niklaus Mueller 1 & Michael Erlanger 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Age-related macular degeneration (AMD) is one of the leading causes of blindness in the industrialized world, affecting over 8 million patients in the United State alone. While the wet (exudative) form of the disease is treated with intraocular injections, there are currently no approved therapies available for the dry (non-exudative) form of the disease which often affects both eyes in patients with AMD. Current research has focused on developing drugs that can be injected into the eye, but the treatment burden associated with monthly injections limits the effectiveness of this approach. Hence, there is a pressing need for a long-term therapeutic solution for patients suffering from this blinding disease. We detail a novel implantable intraocular device, which adsorbs and traps complement factors associated with AMD. In this study, we tested a novel approach by dialyzing proteins from the vitreous using biocompatible implants composed of a nanopore polyacrylonitrile polymer membrane. Preliminary in vitro and in vivo studies demonstrate a high affinity and capacity for complement protein absorption. After a three-month implantation in New Zealand White Cross rabbits, the implant demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology. These studies demonstrate that prolonged CF suppression intraocularly may be accomplished with a nanopore polymer membrane. Keywords Retina . Macular degeneration . Complement factors . Intravitreal drugs
1 Introduction Age related macular degeneration (AMD) is currently the leading cause of blindness in the developed world. (Congdon et al. 2004; Velez-Montoya et al. 2014) Clinically, there are two forms of the disease: dry (non-exudative) and wet (exudative). The exudative form is characterized by pathological neovascularization which is currently treated with intravitreal injections which target the cytokine vascular endothelial growth factor (VEGF) (Gohel et al. 2008). Patients are typically affected first by the dry form, which continues to affect vision even if the wet form develops. The pathogenesis of dry AMD is not completely understood, which limits the availability of current treatment options (Fig. 1). The immune system, specifically the alternative complement pathway, has been shown to play a role in the pathogenesis of AMD (Anderson et al. 2010; * Jeffrey L. Olson [email protected] 1
Sue Anschutz-Rodgers Eye Center, Department of Ophthalmology, University of Colorado School of Medicine, 1675 Aurora Court, Mailstop F731, Aurora, CO 80045, USA
Calippe et al. 2017; Levy et al. 2015). Elevated levels of alternative pathway complement factors, including Complement Factor D (CFD), have been found in the serum of patients with AMD (Scholl et al. 2008; Stanton e
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