Karl E Kador1, Haneen S Alsehli2, Allison N Zindell3, Lung W Lau4, Fotios M Andreopoulos5, Brant D Watson6, Jeffrey L Goldberg7. 1. 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. 2. 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. 3. 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. 4. Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, FL 33136, USA. 5. 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. 6. 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. 7. 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.
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.
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 n class="Gene">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.
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