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Updated: Apr 24, 2026
Engineering Transplantation-suitable Retinal Pigment Epithelium Tissue Derived from Human Embryonic Stem Cells
Published on: September 6, 2018
Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold
Karl E Kador1, Haneen S Alsehli2, Allison N Zindell3
1Shiley 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.
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.
Insights
Researchers developed a novel scaffold to guide retinal ganglion cells (RGCs) using immobilized Netrin-1. This technique improves RGC axon growth, offering potential for treating optic nerve diseases like glaucoma.
Area of Science:
- Neuroscience
- Biomaterials Science
- Regenerative Medicine
Background:
- Retinal ganglion cell (RGC) dysfunction underlies optic neuropathies.
- Current cell transplantation therapies are limited by RGCs' inability to navigate the retina.
- Developmental guidance cues for RGCs are often downregulated in adulthood.
Purpose of the Study:
- To develop a scaffold that guides RGC axonal growth towards the optic nerve head.
- To investigate the efficacy of immobilized Netrin-1 gradients in directing RGCs.
- To enhance the potential of cell-based therapies for optic neuropathies.
Main Methods:
- Immobilization of Netrin-1 onto a radial electrospun scaffold using UV-initiated crosslinking.
- Creation of a Netrin-1 protein gradient on the scaffold.
- Assessment of RGC polarization and axonal growth direction on the scaffold.
Main Results:
- Netrin-gradient scaffolds successfully guided RGC axonal growth.
- The percentage of RGCs with a single axon increased.
- Polarization of RGCs towards the scaffold center improved significantly (31% to 52%).
Conclusions:
- Immobilized Netrin-1 gradients on radial scaffolds promote directed RGC axon growth.
- This approach mimics developmental guidance cues for the optic nerve head.
- The technology shows promise for improving cell transplant therapies for glaucoma and other optic neuropathies.
