Optic Nerve Regeneration: How Will We Get There?

Overview

Journal J Neuroophthalmol

Specialties Neurology
Ophthalmology

Date 2020 Apr 14

PMID 32282513

Citations 10

Authors

Kimberly K Gokoffski

Phillip Lam

Basheer F Alas

Micalla G Peng

Heidi R R Ansorge

Affiliations

Soon will be listed here.

Abstract

Background: Restoration of vision in patients blinded by advanced optic neuropathies requires technologies that can either 1) salvage damaged and prevent further degeneration of retinal ganglion cells (RGCs), or 2) replace lost RGCs.

Evidence Acquisition: Review of scientific literature.

Results: In this article, we discuss the different barriers to cell-replacement based strategies for optic nerve regeneration and provide an update regarding what progress that has been made to overcome them. We also provide an update on current stem cell-based therapies for optic nerve regeneration.

Conclusions: As neuro-regenerative and cell-transplantation based strategies for optic nerve regeneration continue to be refined, researchers and clinicians will need to work together to determine who will be a good candidate for such therapies.

Citing Articles

Electric field stimulation directs target-specific axon regeneration and partial restoration of vision after optic nerve crush injury.

Kim T, Iseri E, Peng M, Medvidovic S, Silliman T, Pahlavan P PLoS One. 2025; 20(1):e0315562.

PMID: 39787061 PMC: 11717274. DOI: 10.1371/journal.pone.0315562.

Whole-eye transplantation: Current challenges and future perspectives.

Scarabosio A, Surico P, Tereshenko V, Singh R, Salati C, Spadea L World J Transplant. 2024; 14(2):95009.

PMID: 38947970 PMC: 11212585. DOI: 10.5500/wjt.v14.i2.95009.

Neuroprotective effects and mechanisms of action of artemisinin in retinal ganglion cells in a mouse model of traumatic optic neuropathy.

Zhou S, Li W, Lv R, Zhang M, Liu W Heliyon. 2024; 10(11):e31378.

PMID: 38828288 PMC: 11140598. DOI: 10.1016/j.heliyon.2024.e31378.

Uncovering the Genetics and Physiology behind Optic Neuritis.

Negro I, Pauletto G, Verriello L, Spadea L, Salati C, Ius T Genes (Basel). 2023; 14(12).

PMID: 38137014 PMC: 10742654. DOI: 10.3390/genes14122192.

Recent Advances of Adipose-Tissue-Derived Mesenchymal Stem Cell-Based Therapy for Retinal Diseases.

Finocchio L, Zeppieri M, Gabai A, Spadea L, Salati C J Clin Med. 2023; 12(22).

PMID: 38002628 PMC: 10672618. DOI: 10.3390/jcm12227015.

References

Sluch V, Davis C, Ranganathan V, Kerr J, Krick K, Martin R . Differentiation of human ESCs to retinal ganglion cells using a CRISPR engineered reporter cell line. Sci Rep. 2015; 5:16595. PMC: 4643248. DOI: 10.1038/srep16595. View

Cen L, Luo J, Geng Y, Zhang M, Pang C, Cui Q . Long-term survival and axonal regeneration of retinal ganglion cells after optic nerve transection and a peripheral nerve graft. Neuroreport. 2012; 23(11):692-7. DOI: 10.1097/WNR.0b013e328355f1d6. View

Schwab M . Repairing the injured spinal cord. Science. 2002; 295(5557):1029-31. DOI: 10.1126/science.1067840. View

Sun F, He Z . Neuronal intrinsic barriers for axon regeneration in the adult CNS. Curr Opin Neurobiol. 2010; 20(4):510-8. PMC: 2911501. DOI: 10.1016/j.conb.2010.03.013. View

Li Y, Schlamp C, Nickells R . Experimental induction of retinal ganglion cell death in adult mice. Invest Ophthalmol Vis Sci. 1999; 40(5):1004-8. View

Kuwahara A, Ozone C, Nakano T, Saito K, Eiraku M, Sasai Y . Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nat Commun. 2015; 6:6286. DOI: 10.1038/ncomms7286. View

Meyer J, Howden S, Wallace K, Verhoeven A, Wright L, Capowski E . Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells. 2011; 29(8):1206-18. PMC: 3412675. DOI: 10.1002/stem.674. View

Ou Y, Jo R, Ullian E, Wong R, Santina L . Selective Vulnerability of Specific Retinal Ganglion Cell Types and Synapses after Transient Ocular Hypertension. J Neurosci. 2016; 36(35):9240-52. PMC: 5005727. DOI: 10.1523/JNEUROSCI.0940-16.2016. View

Yiu G, He Z . Glial inhibition of CNS axon regeneration. Nat Rev Neurosci. 2006; 7(8):617-27. PMC: 2693386. DOI: 10.1038/nrn1956. View

10.

Singhal S, Lawrence J, Bhatia B, Ellis J, Kwan A, Macneil A . Chondroitin sulfate proteoglycans and microglia prevent migration and integration of grafted Müller stem cells into degenerating retina. Stem Cells. 2008; 26(4):1074-82. DOI: 10.1634/stemcells.2007-0898. View

11.

Merrill D, Bikson M, Jefferys J . Electrical stimulation of excitable tissue: design of efficacious and safe protocols. J Neurosci Methods. 2005; 141(2):171-98. DOI: 10.1016/j.jneumeth.2004.10.020. View

12.

Bull N, Limb G, Martin K . Human Müller stem cell (MIO-M1) transplantation in a rat model of glaucoma: survival, differentiation, and integration. Invest Ophthalmol Vis Sci. 2008; 49(8):3449-56. DOI: 10.1167/iovs.08-1770. View

13.

Benowitz L, He Z, Goldberg J . Reaching the brain: Advances in optic nerve regeneration. Exp Neurol. 2016; 287(Pt 3):365-373. DOI: 10.1016/j.expneurol.2015.12.015. View

14.

Yang T, Chuang J, Buddhakosai W, Wu W, Lee C, Chen W . Elongation of Axon Extension for Human iPSC-Derived Retinal Ganglion Cells by a Nano-Imprinted Scaffold. Int J Mol Sci. 2017; 18(9). PMC: 5618661. DOI: 10.3390/ijms18092013. View

15.

Volkner M, Zschatzsch M, Rostovskaya M, Overall R, Busskamp V, Anastassiadis K . Retinal Organoids from Pluripotent Stem Cells Efficiently Recapitulate Retinogenesis. Stem Cell Reports. 2016; 6(4):525-538. PMC: 4834051. DOI: 10.1016/j.stemcr.2016.03.001. View

16.

Singhal S, Bhatia B, Jayaram H, Becker S, Jones M, Cottrill P . Human Müller glia with stem cell characteristics differentiate into retinal ganglion cell (RGC) precursors in vitro and partially restore RGC function in vivo following transplantation. Stem Cells Transl Med. 2012; 1(3):188-99. PMC: 3659849. DOI: 10.5966/sctm.2011-0005. View

17.

Inatani M, Honjo M, Otori Y, Oohira A, Kido N, Tano Y . Inhibitory effects of neurocan and phosphacan on neurite outgrowth from retinal ganglion cells in culture. Invest Ophthalmol Vis Sci. 2001; 42(8):1930-8. View

18.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

19.

Ackman J, Crair M . Role of emergent neural activity in visual map development. Curr Opin Neurobiol. 2014; 24(1):166-75. PMC: 3957181. DOI: 10.1016/j.conb.2013.11.011. View

20.

Li M, Yu J, Tilgner K, Ong S, Koike-Yusa H, Yusa K . Genome-wide CRISPR-KO Screen Uncovers mTORC1-Mediated Gsk3 Regulation in Naive Pluripotency Maintenance and Dissolution. Cell Rep. 2018; 24(2):489-502. PMC: 6057492. DOI: 10.1016/j.celrep.2018.06.027. View