Paying attention to the basic research of optic nerve protection and regeneration, and promote its clinical transformation_Chinese Journal of Ocular Fundus Diseases

Authors：

 Zhong Yong , Lu Yuezhu

Department of Ophthalmology, Peking Union Medical College Hospital, Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Science, Beijing 100730, China;

Corresponding author：

Zhong Yong, Email: yzhong_eye@163.com

Keywords：

Optic neuropathies; Retinal ganglion cells; Neuroprotection; Axonal regeneration; Stem cells; Gene therapy; Editorial

DOI：

10.3760/cma.j.cn511434-20231112-00454

Video：

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Abstract Full text Figures/Tables Video References Cited by

Primary or secondary death of retinal ganglion cells (RGC) is a common outcome in various optic neuropathies, often resulting in severe visual damage. The inherent characteristics of RGC include the continuous upregulation of intracellular growth-inhibitory transcription factors and the downregulation of growth-inducing transcription factors during cell differentiation. Additionally, the external inhibitory microenvironment following RGC damage, including oxidative stress, chronic inflammation, lack of neurotrophic factors, high expression of myelin proteins, and the formation of glial scars, all restrict axonal regeneration. Both intrinsic and extrinsic factors lead to the death of damaged RGC and hinder axonal regeneration. Various neuroprotective agents and methods attempt to promote neuroprotection and axonal regeneration from both intrinsic and extrinsic aspects, and well knowledge of these neuroprotective strategies is of significant importance for promoting the neuroprotective experimental research and facilitating its translation into clinical practice.

Citation： Zhong Yong, Lu Yuezhu. Paying attention to the basic research of optic nerve protection and regeneration, and promote its clinical transformation. Chinese Journal of Ocular Fundus Diseases, 2023, 39(11): 883-886. doi: 10.3760/cma.j.cn511434-20231112-00454 Copy

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9.	Lou X, Hu Y, Zhang H, et al. Polydopamine nanoparticles attenuate retina ganglion cell degeneration and restore visual function after optic nerve injury[J]. J Nanobiotechnology, 2021, 19(1): 436. DOI: 10.1186/s12951-021-01199-3.
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19.	Sun F, Park KK, Belin S, et al. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3[J]. Nature, 2011, 480(7377): 372-375. DOI: 10.1038/nature10594.
20.	de Lima S, Koriyama Y, Kurimoto T, et al. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors[J]. Proc Natl Acad Sci USA, 2012, 109(23): 9149-9154. DOI: 10.1073/pnas.1119449109.
21.	Apara A, Galvao J, Wang Y, et al. KLF9 and JNK3 interact to suppress axon regeneration in the adult CNS[J]. J Neurosci, 2017, 37(40): 9632-9644. DOI: 10.1523/JNEUROSCI.0643-16.2017.
22.	Wang XW, Li Q, Liu CM, et al. Lin28 signaling supports mammalian PNS and CNS axon regeneration[J]. Cell Rep, 2018, 24(10): 2540-2552. DOI: 10.1016/j.celrep.2018.07.105.
23.	Tran NM, Shekhar K, Whitney IE, et al. Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes[J]. Neuron, 2019, 104(6): 1039-1055. DOI: 10.1016/j.neuron.2019.11.006.
24.	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072. DOI: 10.1016/j.cell.2012.03.042.
25.	Guo M, Zhu Y, Shi Y, et al. Inhibition of ferroptosis promotes retina ganglion cell survival in experimental optic neuropathies[J/OL]. Redox Biol, 2022, 58: 102541[2022-11-15]. https://pubmed.ncbi.nlm.nih.gov/36413918/. DOI: 10.1016/j.redox.2022.102541.
26.	Yao Y, Xu Y, Liang JJ, et al. Longitudinal and simultaneous profiling of 11 modes of cell death in mouse retina post-optic nerve injury[J/OL]. Exp Eye Res, 2022, 222: 109159[2022-06-23]. https://pubmed.ncbi.nlm.nih.gov/35753433/. DOI: 10.1016/j.exer.2022.109159.

1. Moore DL, Blackmore MG, Hu Y, et al. KLF family members regulate intrinsic axon regeneration ability[J]. Science, 2009, 326(5950): 298-301. DOI: 10.1126/science.1175737.
2. Zhong Y, Shen X, Liu X, et al. The early effect of nerve growth factor in the management of serious optic nerve contusion[J]. Clin Exp Optom, 2010, 93(6): 466-470. DOI: 10.1111/j.1444-0938.2010.00523.x.
3. Mesentier-Louro LA, Rosso P, Carito V, et al. Nerve growth factor role on retinal ganglion cell survival and axon regrowth: effects of ocular administration in experimental model of optic nerve injury[J]. Mol Neurobiol, 2019, 56(2): 1056-1069. DOI: 10.1007/s12035-018-1154-1.
4. Lambiase A, Aloe L, Centofanti M, et al. Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: implications for glaucoma[J]. Proc Natl Acad Sci USA, 2009, 106(32): 13469-13474. DOI: 10.1073/pnas.0906678106.
5. Sánchez-Migallón MC, Valiente-Soriano FJ, Nadal-Nicolás FM, et al. Apoptotic retinal ganglion cell death after optic nerve transection or crush in mice: delayed RGC loss with BDNF or a caspase 3 inhibitor[J]. Invest Ophthalmol Vis Sci, 2016, 57(1): 81-93. DOI: 10.1167/iovs.15-17841.
6. Laughter MR, Bardill JR, Ammar DA, et al. Injectable neurotrophic factor delivery system supporting retinal ganglion cell survival and regeneration following optic nerve crush[J]. ACS Biomater Sci Eng, 2018, 4(9): 3374-3383. DOI: 10.1021/acsbiomaterials.8b00803.
7. Dulz S, Bassal M, Flachsbarth K, et al. Intravitreal co-administration of GDNF and CNTF confers synergistic and long-lasting protection against injury-induced cell death of retinal ganglion cells in mice[J/OL]. Cells, 2020, 9(9): 2082[2020-09-11]. https://pubmed.ncbi.nlm.nih.gov/32932933/. DOI: 10.3390/cells9092082.
8. Williams PA, Harder JM, Foxworth NE, et al. Vitamin B₃ modulates mitochondrial vulnerability and prevents glaucoma in aged mice[J]. Science, 2017, 355(6326): 756-760. DOI: 10.1126/science.aal0092.
9. Lou X, Hu Y, Zhang H, et al. Polydopamine nanoparticles attenuate retina ganglion cell degeneration and restore visual function after optic nerve injury[J]. J Nanobiotechnology, 2021, 19(1): 436. DOI: 10.1186/s12951-021-01199-3.
10. Tansley K. The development of the rat eye in graft[J]. J Exp Biol, 1946, 22: 221-224. DOI: 10.1242/jeb.22.3-4.221.
11. Oswald J, Kegeles E, Minelli T, et al. Transplantation of miPSC/mESC-derived retinal ganglion cells into healthy and glaucomatous retinas[J]. Mol Ther Methods Clin Dev, 2021, 21: 180-198. DOI: 10.1016/j.omtm.2021.03.004.
12. Divya MS, Rasheed VA, Schmidt T, et al. Intraocular injection of ES cell-derived neural progenitors improve visual function in retinal ganglion cell-depleted mouse models[J/OL]. Front Cell Neurosci, 2017, 11: 295[2017-09-20]. https://pubmed.ncbi.nlm.nih.gov/28979193/. DOI: 10.3389/fncel.2017.00295.
13. Chao JR, Lamba DA, Klesert TR, et al. Transplantation of human embryonic stem cell-derived retinal cells into the subretinal space of a non-human primate[J]. Transl Vis Sci Technol, 2017, 6(3): 4. DOI: 10.1167/tvst.6.3.4.
14. Mead B, Amaral J, Tomarev S. Mesenchymal stem cell-derived small extracellular vesicles promote neuroprotection in rodent models of glaucoma[J]. Invest Ophthalmol Vis Sci, 2018, 59(2): 702-714. DOI: 10.1167/iovs.17-22855.
15. Mead B, Tomarev S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms[J]. Stem Cells Transl Med, 2017, 6(4): 1273-1285. DOI: 10.1002/sctm.16-0428.
16. Cui Y, Liu C, Huang L, et al. Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury[J/OL]. Exp Cell Res, 2021, 407(1): 112792[2021-08-27]. https://pubmed.ncbi.nlm.nih.gov/34454924/. DOI: 10.1016/j.yexcr.2021.112792.
17. Park KK, Liu K, Hu Y, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway[J]. Science, 2008, 322(5903): 963-966. DOI: 10.1126/science.1161566.
18. Smith PD, Sun F, Park KK, et al. SOCS3 deletion promotes optic nerve regeneration in vivo[J]. Neuron, 2009, 64(5): 617-623. DOI: 10.1016/j.neuron.2009.11.021.
19. Sun F, Park KK, Belin S, et al. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3[J]. Nature, 2011, 480(7377): 372-375. DOI: 10.1038/nature10594.
20. de Lima S, Koriyama Y, Kurimoto T, et al. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors[J]. Proc Natl Acad Sci USA, 2012, 109(23): 9149-9154. DOI: 10.1073/pnas.1119449109.
21. Apara A, Galvao J, Wang Y, et al. KLF9 and JNK3 interact to suppress axon regeneration in the adult CNS[J]. J Neurosci, 2017, 37(40): 9632-9644. DOI: 10.1523/JNEUROSCI.0643-16.2017.
22. Wang XW, Li Q, Liu CM, et al. Lin28 signaling supports mammalian PNS and CNS axon regeneration[J]. Cell Rep, 2018, 24(10): 2540-2552. DOI: 10.1016/j.celrep.2018.07.105.
23. Tran NM, Shekhar K, Whitney IE, et al. Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes[J]. Neuron, 2019, 104(6): 1039-1055. DOI: 10.1016/j.neuron.2019.11.006.
24. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072. DOI: 10.1016/j.cell.2012.03.042.
25. Guo M, Zhu Y, Shi Y, et al. Inhibition of ferroptosis promotes retina ganglion cell survival in experimental optic neuropathies[J/OL]. Redox Biol, 2022, 58: 102541[2022-11-15]. https://pubmed.ncbi.nlm.nih.gov/36413918/. DOI: 10.1016/j.redox.2022.102541.
26. Yao Y, Xu Y, Liang JJ, et al. Longitudinal and simultaneous profiling of 11 modes of cell death in mouse retina post-optic nerve injury[J/OL]. Exp Eye Res, 2022, 222: 109159[2022-06-23]. https://pubmed.ncbi.nlm.nih.gov/35753433/. DOI: 10.1016/j.exer.2022.109159.

Chinese Journal of Ocular Fundus Diseases

Paying attention to the basic research of optic nerve protection and regeneration, and promote its clinical transformation

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