title: Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold.
abstract: Cell transplantation therapies to treat diseases related to dysfunction of retinal ganglion cells (RGCs) are limited in part by an inability to navigate to the optic nerve head within the retina. During development, RGCs are guided by a series of neurotrophic factors and guidance cues; however, these factors and their receptors on the RGCs are developmentally regulated and often not expressed during adulthood. Netrin-1 is a guidance factor capable of guiding RGCs in culture and relevant to guiding RGC axons toward the optic nerve head in vivo. Here we immobilized Netrin-1 using UV-initiated crosslinking to form a gradient capable of guiding the axonal growth of RGCs on a radial electrospun scaffold. Netrin-gradient scaffolds promoted both the percentage of RGCs polarized with a single axon, and also the percentage of cells polarized toward the scaffold center, from 31% to 52%. Thus, an immobilized protein gradient on a radial electrospun scaffold increases RGC axon growth in a direction consistent with developmental optic nerve head guidance, and may prove beneficial for use in cell transplant therapies for the treatment of glaucoma and other optic neuropathies.
authors.affiliation: Shiley Eye Center and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92093, USA; Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, FL 33136, USA.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Kador
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, FL 33136, USA; Department of Biomedical Sciences, Barry University, Miami Shores, FL 33161, USA.
authors.forename: Haneen S
authors.initials: HS
authors.lastname: Alsehli
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, FL 33136, USA; Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33136, USA.
authors.forename: Allison N
authors.initials: AN
authors.lastname: Zindell
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, FL 33136, USA.
authors.forename: Lung W
authors.initials: LW
authors.lastname: Lau
authors.affiliation: Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33136, USA; Department of Surgery, Miller School of Medicine, University of Miami, FL 33136, USA.
authors.forename: Fotios M
authors.initials: FM
authors.lastname: Andreopoulos
authors.affiliation: Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33136, USA; Department of Neurology, Miller School of Medicine, University of Miami, FL 33136, USA.
authors.forename: Brant D
authors.initials: BD
authors.lastname: Watson
authors.affiliation: Shiley Eye Center and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92093, USA; Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, FL 33136, USA. Electronic address: jlgoldberg@ucsd.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Goldberg
mesh_terms: D000327:Adsorption; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004867:Equipment Design; D019544:Equipment Failure Analysis; D048091:Guided Tissue Regeneration / Q000295:instrumentation*; D051379:Mice; D009414:Nerve Growth Factors / Q000737:chemistry* / Q000493:pharmacokinetics*; D000075388:Netrin-1; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000502:physiology*; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D020099:Coated Materials, Biocompatible; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1
keywords: Axon guidance; Netrin; Protein immobilization; Retinal ganglion cell