Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold

Karl E. Kador, Haneen S. Alsehli, Allison N. Zindell, Lung W. Lau, Fotios M Andreopoulos, Brant D. Watson, Jeffrey L. Goldberg

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4939-4946
Number of pages8
JournalActa Biomaterialia
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2014

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Keywords

  • Axon guidance
  • Netrin
  • Protein immobilization
  • Retinal ganglion cell

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

Cite this

Kador, K. E., Alsehli, H. S., Zindell, A. N., Lau, L. W., Andreopoulos, F. M., Watson, B. D., & Goldberg, J. L. (2014). Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold. Acta Biomaterialia, 10(12), 4939-4946. https://doi.org/10.1016/j.actbio.2014.08.032