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Karen Chang, Kin-Sang Cho, Jhih-Guang Wu, Chia-Yu Lin, Shyh-Chyang Luo, Ta-Ching Chen, Wei-Fang Su, Min-Huey Chen, Dong Feng Chen; A bioengineering approach for promoting retina ganglion cell axon regeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1855.
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© ARVO (1962-2015); The Authors (2016-present)
The optic nerve, as part of the central nerve system, transmits visual information from the retina to the brain. Glaucoma and other optic neuropathies lead to permanent vision loss due to progressive degeneration of retinal ganglion cells (RGCs). While cell therapy presents as a potential treatment for neurodegeneration, it remains challenging due to the limited ability of transplanted RGCs to survive, integrate into the retina, and extend long neurites through the optic nerve. The purpose of this study is to develop a bioengineered scaffold that promotes directed axon growth and may serve as a feasible treatment for optic nerve damage or degeneration.
Chemical synthesized polypeptide (CSPD) scaffolds were fabricated by electrospinning with different alignments; a commonly used biocompatible scaffold, polycaprolactone (PCL), was selected as a comparative control. By further incorporating polyglutamic acid into CSPD, a new scaffold, CSPD-G was developed. To investigate the biocompatibility of those scaffolds, retinal explant or primary RGCs isolated from postnatal day 0-1 (P0-1) C57BL/6 mouse pups were cultured on glass, aligned or isotropic PCL and CSPD with matrigel coating for 3-5 days. The rate of cell survival, neurite outgrowth, neurite lengths, and the angles of neurite extension were analyzed and quantified.
The aligned and isotropic scaffolds of PCL and CSPD featured similar 3D fibrous structures under scanning electron microscopy (SEM). Compared to glass and PCL controls, CSPD scaffolds supported primary RGC survival and promoted much more robust growth of long neurites in both explants and dissociated cell cultures (p<0.01). The aligned CSPD scaffold drove directed nerve elongations along the direction of fibers, guiding neurites growing towards the same orientation.
CSPD presents a permissive biomaterial that drives robust and directed axon growth in both primary cultured RGCs and retinal explants. Future studies to investigate the mechanisms underlying CSPD-induced nerve growth are needed.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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