A Review on the Application of Stem Cell Secretome in the Protection and Regeneration of Retinal Ganglion Cells; a Clinical Prospect in the Treatment of Optic Neuropathies

References

• Smith C, Vianna J, Chauhan B. Assessing retinal ganglion cell damage. Eye (Lond). 2017;31(2):209–217. doi:10.1038/eye.2016.295.
   PubMed Web of Science ®Google Scholar
• Shen J, Wang Y, Yao K. Protection of retinal ganglion cells in glaucoma: current status and future. Exp Eye Res. 2021;205:108506. doi:10.1016/j.exer.2021.108506.
   PubMed Web of Science ®Google Scholar
• Song W, Huang P, Zhang C. Neuroprotective therapies for glaucoma. Drug Des Devel Ther. 2015;9:1469–1479. doi:10.2147/DDDT.S80594.
   PubMed Web of Science ®Google Scholar
• Fu L, Kwok SS, Chan YK, Ming Lai JS, Pan W, Nie L, Shih KC. Therapeutic strategies for attenuation of retinal ganglion cell injury in optic neuropathies: concepts in translational research and therapeutic implications. Biomed Res Int. 2019;2019:8397521. doi:10.1155/2019/8397521.
   PubMedGoogle Scholar
• Kumar P, Kandoi S, Misra R, Vijayalakshmi S, Rajagopal K, Verma RS. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev. 2019;46:1–9. doi:10.1016/j.cytogfr.2019.04.002.
   PubMed Web of Science ®Google Scholar
• Pitt JM, Kroemer G, Zitvogel L. Extracellular vesicles: masters of intercellular communication and potential clinical interventions. J Clin Invest. 2016;126(4):1139–1143. doi:10.1172/JCI87316.
   PubMed Web of Science ®Google Scholar
• Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 2013;32(3–4):623–642. doi:10.1007/s10555-013-9441-9.
   PubMed Web of Science ®Google Scholar
• Johnstone R, Mathew A, Mason A, Teng K. Exosome formation during maturation of mammalian and avian reticulocytes: Evidence that exosome release is a major route for externalization of obsolete membrane proteins. J Cell Physiol. 1991;147(1):27–36. doi:10.1002/jcp.1041470105.
   PubMed Web of Science ®Google Scholar
• Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569–579. doi:10.1038/nri855.
   PubMed Web of Science ®Google Scholar
• Rahimi B, Panahi M, Saraygord-Afshari N, Taheri N, Bilici M, Jafari D, Alizadeh E. The secretome of mesenchymal stem cells and oxidative stress: challenges and opportunities in cell-free regenerative medicine. Mol Biol Rep. 2021;48(7):5607–5619. doi:10.1007/s11033-021-06360-7.
   PubMed Web of Science ®Google Scholar
• Ranganath SH, Levy O, Inamdar MS, Karp JM. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell. 2012;10(3):244–258. doi:10.1016/j.stem.2012.02.005.
   PubMed Web of Science ®Google Scholar
• Wu Y-R, Hashiguchi T, Sho J, Chiou S-H, Takahashi M, Mandai M. Transplanted mouse embryonic stem cell–derived retinal ganglion cells integrate and form synapses in a retinal ganglion cell-depleted mouse model. Invest Ophthalmol Vis Sci. 2021;62(13):26–26. doi:10.1167/iovs.62.13.26.
   Web of Science ®Google Scholar
• Millán-Rivero JE, Nadal-Nicolás FM, García-Bernal D, Sobrado-Calvo P, Blanquer M, Moraleda JM, Vidal-Sanz M, Agudo-Barriuso M. Human Wharton’s Jelly mesenchymal stem cells protect axotomized rat retinal ganglion cells via secretion of anti-inflammatory and neurotrophic factors. Sci. Rep. 2018;8(1):1–14.
   PubMed Web of Science ®Google Scholar
• Nemati S, Seiedrazizadeh Z, Simorgh S, Hesaraki M, Kiani S, Javan M, Pakdel F, Satarian L. Mouse degenerating optic axons survived by human embryonic stem cell-derived neural progenitor cells. Cell J. 2022;24(3):120–126. doi:10.22074/cellj.2022.7873.
   PubMed Web of Science ®Google Scholar
• Jha K, Pentecost M, Lenin R, Klaic L, Elshaer S, Gentry J, Russell J, Beland A, Reiner A, Jotterand V, et al. Concentrated conditioned media from adipose tissue derived mesenchymal stem cells mitigates visual deficits and retinal inflammation following mild traumatic brain injury. IJMS. 2018;19(7):2016. doi:10.3390/ijms19072016.
   Web of Science ®Google Scholar
• Li N, Sarojini H, An J, Wang E. Prosaposin in the secretome of marrow stroma‐derived neural progenitor cells protects neural cells from apoptotic death. J Neurochem. 2010;112(6):1527–1538. doi:10.1111/j.1471-4159.2009.06565.x.
   PubMed Web of Science ®Google Scholar
• Mead B, Ahmed Z, Tomarev S. Mesenchymal stem cell–derived small extracellular vesicles promote neuroprotection in a genetic dba/2j mouse model of glaucoma. Invest Ophthalmol Vis Sci. 2018;59(13):5473–5480. doi:10.1167/iovs.18-25310.
   PubMed Web of Science ®Google Scholar
• Miki T, Lehmann T, Cai H, Stolz DB, Strom SC. Stem cell characteristics of amniotic epithelial cells. Stem Cells. 2005;23(10):1549–1559. doi:10.1634/stemcells.2004-0357.
   PubMed Web of Science ®Google Scholar
• Miki T, Mitamura K, Ross MA, Stolz DB, Strom SC. Identification of stem cell marker-positive cells by immunofluorescence in term human amnion. J Reprod Immunol. 2007;75(2):91–96. doi:10.1016/j.jri.2007.03.017.
   PubMed Web of Science ®Google Scholar
• Adinolfi M, Akle C, McColl I, Fensom A, Tansley L, Connolly P, Hsi B-L, Faulk W, Travers P, Bodmer W. Expression of HLA antigens, β 2-microglobulin and enzymes by human amniotic epithelial cells. Nature. 1982;295(5847):325–327. doi:10.1038/295325a0.
   PubMed Web of Science ®Google Scholar
• Banas R, Miller C, Guzik L, Zeevi A. Amnion-derived multipotent progenitor cells inhibit blood monocyte differentiation into mature dendritic cells. Cell Transplant. 2014;23(9):1111–1125. doi:10.3727/096368913X670165.
   PubMed Web of Science ®Google Scholar
• Banas RA, Trumpower C, Bentlejewski C, Marshall V, Sing G, Zeevi A. Immunogenicity and immunomodulatory effects of amnion-derived multipotent progenitor cells. Hum Immunol. 2008;69(6):321–328. doi:10.1016/j.humimm.2008.04.007.
   PubMed Web of Science ®Google Scholar
• Steed DL, Trumpower C, Duffy D, Smith C, Marshall V, Rupp R, Robson M. Amnion-derived cellular cytokine solution: a physiological combination of cytokines for wound healing. Eplasty. 2008;8:e18.
   PubMedGoogle Scholar
• Grinblat GA, Khan RS, Dine K, Wessel H, Brown L, Shindler KS. Rgc neuroprotection following optic nerve trauma mediated by intranasal delivery of amnion cell secretome. Invest Ophthalmol Vis Sci. 2018;59(6):2470–2477. doi:10.1167/iovs.18-24096.
   PubMed Web of Science ®Google Scholar
• Khan RS, Dine K, Bauman B, Lorentsen M, Lin L, Brown H, Hanson LR, Svitak AL, Wessel H, Brown L. Intranasal delivery of a novel amnion cell secretome prevents neuronal damage and preserves function in a mouse multiple sclerosis model. Sci Rep. 2017;7(1):1–12.
   PubMedGoogle Scholar
• Khan RS, Dine K, Wessel H, Brown L, Shindler KS. Effects of varying intranasal treatment regimens in st266-mediated rgc neuroprotection. J Neuroophthalmol. 2019;39(2):191–199. doi:10.1097/WNO.0000000000000760.
   PubMed Web of Science ®Google Scholar
• Willett K, Khan RS, Dine K, Wessel H, Kirshner ZZ, Sauer JL, Ellis A, Brown LR, Shindler KS. Neuroprotection mediated by st266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells. PLoS One. 2021;16(1):e0243862. doi:10.1371/journal.pone.0243862.
   PubMed Web of Science ®Google Scholar
• Roubelakis MG, Pappa KI, Bitsika V, Zagoura D, Vlahou A, Papadaki HA, Antsaklis A, Anagnou NP. Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells Dev. 2007;16(6):931–952. doi:10.1089/scd.2007.0036.
   PubMed Web of Science ®Google Scholar
• Yan Z-J, Hu Y-Q, Zhang H-T, Zhang P, Xiao Z-Y, Sun X-L, Cai Y-Q, Hu C-C, Xu R-X. Comparison of the neural differentiation potential of human mesenchymal stem cells from amniotic fluid and adult bone marrow. Cell Mol Neurobiol. 2013;33(4):465–475. doi:10.1007/s10571-013-9922-y.
   PubMed Web of Science ®Google Scholar
• Davari M, Soheili Z-S, Ahmadieh H, Sanie-Jahromi F, Ghaderi S, Kanavi MR, Samiei S, Akrami H, Haghighi M, Javidi-Azad F. Amniotic fluid promotes the appearance of neural retinal progenitors and neurons in human RPE cell cultures. Mol. Vis. 2013;33:2330.
   Google Scholar
• Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress t-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, Am Soc Hematol. 2002;99(10):3838–3843. doi:10.1182/blood.v99.10.3838.
   Web of Science ®Google Scholar
• Han H-S, Jun H-S, Utsugi T, Yoon J-W. Molecular role of TGF-β, secreted from a new type of CD4+ suppressor T cell, NY4. 2, in the prevention of autoimmune IDDM in nod mice. J Autoimmun. 1997;10(3):299–307. doi:10.1006/jaut.1997.0137.
   PubMed Web of Science ®Google Scholar
• Harrell CR, Gazdic M, Fellabaum C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Therapeutic potential of amniotic fluid derived mesenchymal stem cells based on their differentiation capacity and immunomodulatory properties. Curr Stem Cell Res Ther. 2019;14(4):327–336. doi:10.2174/1574888X14666190222201749.
   PubMed Web of Science ®Google Scholar
• Balbi C, Piccoli M, Barile L, Papait A, Armirotti A, Principi E, Reverberi D, Pascucci L, Becherini P, Varesio L, et al. First characterization of human amniotic fluid stem cell extracellular vesicles as a powerful paracrine tool endowed with regenerative potential. Stem Cells Transl Med. 2017;6(5):1340–1355. doi:10.1002/sctm.16-0297.
   PubMed Web of Science ®Google Scholar
• Wang L, Wei X. T cell-mediated autoimmunity in glaucoma neurodegeneration. Front Immunol. 2021;12:803485. doi:10.3389/fimmu.2021.803485.
   PubMed Web of Science ®Google Scholar
• Harrell CR, Fellabaum C, Arsenijevic A, Markovic BS, Djonov V, Volarevic V. Therapeutic potential of mesenchymal stem cells and their secretome in the treatment of glaucoma. Stem Cells Int. 2019;2019:7869130. doi:10.1155/2019/7869130.
   PubMed Web of Science ®Google Scholar
• Johnson TV, DeKorver NW, Levasseur VA, Osborne A, Tassoni A, Lorber B, Heller JP, Villasmil R, Bull ND, Martin KR, et al. Identification of retinal ganglion cell neuroprotection conferred by platelet-derived growth factor through analysis of the mesenchymal stem cell secretome. Brain. 2014;137(Pt 2):503–519. doi:10.1093/brain/awt292.
   PubMed Web of Science ®Google Scholar
• Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR. Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma. Invest Ophthalmol Vis Sci. 2010;51(4):2051–2059. doi:10.1167/iovs.09-4509.
   PubMed Web of Science ®Google Scholar
• Mead B, Amaral J, Tomarev S. Mesenchymal stem cell–derived small extracellular vesicles promote neuroprotection in rodent models of glaucoma. Invest Ophthalmol Vis Sci. 2018;59(2):702–714. doi:10.1167/iovs.17-22855.
   PubMed Web of Science ®Google Scholar
• Na L, Xiao-Rong L, Jia-Qin Y. Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia/reperfusion. Graefes Arch Clin Exp Ophthalmol. 2009;247(4):503–514. doi:10.1007/s00417-008-1009-y.
   PubMed Web of Science ®Google Scholar
• Yu S, Tanabe T, Dezawa M, Ishikawa H, Yoshimura N. Effects of bone marrow stromal cell injection in an experimental glaucoma model. Biochem Biophys Res Commun. 2006;344(4):1071–1079. doi:10.1016/j.bbrc.2006.03.231.
   PubMed Web of Science ®Google Scholar
• Zhao T, Li Y, Tang L, Li Y, Fan F, Jiang B. Protective effects of human umbilical cord blood stem cell intravitreal transplantation against optic nerve injury in rats. Graefes Arch Clin Exp Ophthalmol. 2011;249(7):1021–1028. doi:10.1007/s00417-011-1635-7.
   PubMed Web of Science ®Google Scholar
• Zwart I, Hill AJ, Al-Allaf F, Shah M, Girdlestone J, Sanusi AB, Mehmet H, Navarrete R, Navarrete C, Jen L-S. Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model. Exp Neurol. 2009;216(2):439–448. doi:10.1016/j.expneurol.2008.12.028.
   PubMed Web of Science ®Google Scholar
• Mead B, Tomarev S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms. Stem Cells Transl Med. 2017;6(4):1273–1285. doi:10.1002/sctm.16-0428.
   PubMed Web of Science ®Google Scholar
• Mead B, Tomarev S. Extracellular vesicle therapy for retinal diseases. Prog Retin Eye Res. 2020;79:100849. doi:10.1016/j.preteyeres.2020.100849.
   PubMed Web of Science ®Google Scholar
• Li H, Su Y, Wang F, Tao F. Exosomes: a new way of protecting and regenerating optic nerve after injury. Hum. Cell. 2022;35:1–8.
   PubMed Web of Science ®Google Scholar
• Li R, Jin Y, Li Q, Sun X, Zhu H, Cui H. MiR-93-5p targeting PTEN regulates the NMDA-induced autophagy of retinal ganglion cells via AKT/mTOR pathway in glaucoma. Biomed Pharmacother. 2018;100:1–7. doi:10.1016/j.biopha.2018.01.044.
   PubMed Web of Science ®Google Scholar
• Mak HK, Yung JSY, Weinreb RN, Ng SH, Cao X, Ho TYC, Ng TK, Chu WK, Yung WH, Choy KW, et al. Microrna-19a-PTEN axis is involved in the developmental decline of axon regenerative capacity in retinal ganglion cells. Mol Ther Nucleic Acids. 2020;21:251–263. doi:10.1016/j.omtn.2020.05.031.
   PubMedGoogle Scholar
• Marler KJ, Suetterlin P, Dopplapudi A, Rubikaite A, Adnan J, Maiorano NA, Lowe AS, Thompson ID, Pathania M, Bordey A, et al. BDNF promotes axon branching of retinal ganglion cells via miRNA-132 and p250gap. J Neurosci. 2014;34(3):969–979. doi:10.1523/JNEUROSCI.1910-13.2014.
   PubMed Web of Science ®Google Scholar
• Zhang Q-l, Wang W, Li J, Tian S-Y, Zhang T-Z. Decreased mIR-187 induces retinal ganglion cell apoptosis through upregulating SMAD7 in glaucoma. Biomed Pharmacother. 2015;75:19–25. doi:10.1016/j.biopha.2015.08.028.
   PubMed Web of Science ®Google Scholar
• Zhang Q, He C, Li R, Ke Y, Sun K, Wang J. mIR-708 and mIR-335-3p inhibit the apoptosis of retinal ganglion cells through suppressing autophagy. J Mol Neurosci. 2021;71(2):284–292. doi:10.1007/s12031-020-01648-y.
   PubMed Web of Science ®Google Scholar
• Nie X-G, Fan D-S, Huang Y-X, He Y-Y, Dong B-L, Gao F. Downregulation of microrna-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/AKT signaling pathway in mice with glaucoma. Am J Physiol Cell Physiol. 2018;315(6):C839–C849. doi:10.1152/ajpcell.00324.2017.
   PubMed Web of Science ®Google Scholar
• Yang J, Wang N, Luo X. Intraocular mIR-211 exacerbates pressure-induced cell death in retinal ganglion cells via direct repression of FRS2 signaling. Biochem Biophys Res Commun. 2018;503(4):2984–2992. doi:10.1016/j.bbrc.2018.08.082.
   PubMed Web of Science ®Google Scholar
• Harrell CR, Simovic Markovic B, Fellabaum C, Arsenijevic A, Djonov V, Arsenijevic N, Volarevic V. Therapeutic potential of mesenchymal stem cell-derived exosomes in the treatment of eye diseases. Stem Cells Transl Med. 2018;2(2):47–57.
   Google Scholar
• Li X, Wang Q, Ren Y, Wang X, Cheng H, Yang H, Wang B. Tetramethylpyrazine protects retinal ganglion cells against H2O2-induced damage via the microRNA-182/mitochondrial pathway. Int J Mol Med. 2019;44(2):503–512. doi:10.3892/ijmm.2019.4214.
   PubMed Web of Science ®Google Scholar
• Cui Y, Liu C, Huang L, Chen J, Xu N. Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury. Exp Cell Res. 2021;407(1):112792. doi:10.1016/j.yexcr.2021.112792.
   PubMed Web of Science ®Google Scholar
• Mathew B, Torres LA, Gamboa Acha L, Tran S, Liu A, Patel R, Chennakesavalu M, Aneesh A, Huang C-C, Feinstein DL, et al. Uptake and distribution of administered bone marrow mesenchymal stem cell extracellular vesicles in retina. Cells. 2021;10(4):730. doi:10.3390/cells10040730.
   PubMed Web of Science ®Google Scholar
• Mathew B, Ravindran S, Liu X, Torres L, Chennakesavalu M, Huang C-C, Feng L, Zelka R, Lopez J, Sharma M, et al. Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion. Biomaterials. 2019;197:146–160. doi:10.1016/j.biomaterials.2019.01.016.
   PubMed Web of Science ®Google Scholar
• Noda S, Kawashima N, Yamamoto M, Hashimoto K, Nara K, Sekiya I, Okiji T. Effect of cell culture density on dental pulp-derived mesenchymal stem cells with reference to osteogenic differentiation. Sci. Rep. 2019;9(1):1–11.
   PubMed Web of Science ®Google Scholar
• Mead B, Logan A, Berry M, Leadbeater W, Scheven BA. Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells: comparison with human bone marrow and adipose-derived mesenchymal stem cells. PloS One. 2014;9(10):e109305. doi:10.1371/journal.pone.0109305.
   PubMed Web of Science ®Google Scholar
• Mead B, Logan A, Berry M, Leadbeater W, Scheven BA. Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury. Invest Ophthalmol Vis Sci. 2013;54(12):7544–7556. doi:10.1167/iovs.13-13045.
   PubMed Web of Science ®Google Scholar
• Mead B, Logan A, Berry M, Leadbeater W, Scheven BA. Dental pulp stem cells, a paracrine-mediated therapy for the retina. Neural Regen Res. 2014;9(6):577–578. doi:10.4103/1673-5374.130089.
   PubMed Web of Science ®Google Scholar
• Nagamura-Inoue T, He H. Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility. World J Stem Cells. 2014;6(2):195–202. doi:10.4252/wjsc.v6.i2.195.
   PubMedGoogle Scholar
• Lucas-Ruiz F, Galindo-Romero C, García-Bernal D, Norte-Muñoz M, Rodríguez-Ramírez KT, Salinas-Navarro M, Millán-Rivero JE, Vidal-Sanz M, Agudo-Barriuso M. Mesenchymal stromal cell therapy for damaged retinal ganglion cells, is gold all that glitters? Neural Regen Res. 2019;14(11):1851–1857. doi:10.4103/1673-5374.259601.
   PubMed Web of Science ®Google Scholar
• Arslan U. Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: Preliminary clinical results. Stem Cell Res Ther. 2020;11(1):NA–NA.
   Web of Science ®Google Scholar
• Wang Y, Lv J, Huang C, Li X, Chen Y, Wu W, Wu R. Human umbilical cord-mesenchymal stem cells survive and migrate within the vitreous cavity and ameliorate retinal damage in a novel rat model of chronic glaucoma. Stem Cells Int. 2021;2021:1–11. 2021( doi:10.1155/2021/8852517.
   Web of Science ®Google Scholar
• Pan D, Chang X, Xu M, Zhang M, Zhang S, Wang Y, Luo X, Xu J, Yang X, Sun X. Umsc-derived exosomes promote retinal ganglion cells survival in a rat model of optic nerve crush. J Chem Neuroanat. 2019;96:134–139. doi:10.1016/j.jchemneu.2019.01.006.
   PubMed Web of Science ®Google Scholar
• Vidal-Sanz M, Salinas-Navarro M, Nadal-Nicolás FM, Alarcón-Martínez L, Valiente-Soriano FJ, de Imperial JM, Avilés-Trigueros M, Agudo-Barriuso M, Villegas-Pérez MP. Understanding glaucomatous damage: anatomical and functional data from ocular hypertensive rodent retinas. Prog Retin Eye Res. 2012;31(1):1–27. doi:10.1016/j.preteyeres.2011.08.001.
   PubMed Web of Science ®Google Scholar
• Pardue MT, Allen RS. Neuroprotective strategies for retinal disease. Prog Retin Eye Res. 2018;65:50–76. doi:10.1016/j.preteyeres.2018.02.002.
   PubMed Web of Science ®Google Scholar
• Yu B, Shao H, Su C, Jiang Y, Chen X, Bai L, Zhang Y, Li Q, Zhang X, Li X. Exosomes derived from MSCS ameliorate retinal laser injury partially by inhibition of MCP-1. Sci. Rep. 2016;6(1):1–12.
   PubMed Web of Science ®Google Scholar
• Koh K, Park M, Bae ES, Duong V-A, Park J-M, Lee H, Lew H. UBA2 activates Wnt/β-catenin signaling pathway during protection of r28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells. Stem Cell Res Ther. 2020;11(1):1–14.
   PubMed Web of Science ®Google Scholar
• Yan B-j, Wu Z-z, Chong W-h, Li G. l. Construction of a plasmid for human brain-derived neurotrophic factor and its effect on retinal pigment epithelial cell viability. Neural Regen Res. 2016;11(12):1981–1989. doi:10.4103/1673-5374.197142.
   PubMed Web of Science ®Google Scholar
• Yan B, Gao L, Huang Y, Wang X, Lang X, Yan F, Meng B, Sun X, Li G, Wang Y. Exosomes derived from BDNF-expressing 293t attenuate ischemic retinal injury in vitro and in vivo. Aging. 2020;12:1–13. doi:10.18632/aging.202245.
   PubMedGoogle Scholar
• Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8(4):315–317. doi:10.1080/14653240600855905.
   PubMed Web of Science ®Google Scholar
• Hematti P. Human embryonic stem cell–derived mesenchymal stromal cells. Transfusion. 2011;51:138S–144S. doi:10.1111/j.1537-2995.2011.03376.x.
   PubMed Web of Science ®Google Scholar
• Hawkins KE, Corcelli M, Dowding K, Ranzoni AM, Vlahova F, Hau K-L, Hunjan A, Peebles D, Gressens P, Hagberg H, et al. Embryonic stem cell-derived mesenchymal stem cells (MSCS) have a superior neuroprotective capacity over fetal MSCS in the hypoxic-ischemic mouse brain. Stem Cells Transl Med. 2018;7(5):439–449. doi:10.1002/sctm.17-0260.
   PubMed Web of Science ®Google Scholar
• Seyedrazizadeh S-Z, Poosti S, Nazari A, Alikhani M, Shekari F, Pakdel F, Shahpasand K, Satarian L, Baharvand H. Extracellular vesicles derived from human ES-MSCS protect retinal ganglion cells and preserve retinal function in a rodent model of optic nerve injury. Stem Cell Res Ther. 2020;11(1):1–13.
   PubMed Web of Science ®Google Scholar
• Lamba D, Reh TA. Regenerative medicine for diseases of the retina. In Regenerative medicine for diseases of the retina. Principles of regenerative medicine. Cambridge, MA: Academic Press; 2008.
   Google Scholar
• Walshe TE, Leach LL, D'Amore PA. TGF-β signaling is required for maintenance of retinal ganglion cell differentiation and survival. Neuroscience. 2011;189:123–131. doi:10.1016/j.neuroscience.2011.05.020.
   PubMed Web of Science ®Google Scholar
• Bhatia B, Jayaram H, Singhal S, Jones MF, Limb GA. Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye. Exp Eye Res. 2011;93(6):852–861. doi:10.1016/j.exer.2011.09.015.
   PubMed Web of Science ®Google Scholar
• Fischer AJ. Neural regeneration in the chick retina. Prog Retin Eye Res. 2005;24(2):161–182. doi:10.1016/j.preteyeres.2004.07.003.
   PubMed Web of Science ®Google Scholar
• Yang S, Zhou J, Li D. Functions and diseases of the retinal pigment epithelium. Front Pharmacol. 2021;12:1976. doi:10.3389/fphar.2021.727870.
   Web of Science ®Google Scholar
• Sanie-Jahromi F, Nowroozzadeh MH, Khodabandeh Z, Soheili Z-S, Khajehahmadi Z, Emadi Z, Talebnejad MR. Effects of the secretome of human Wharton’s jelly mesenchymal stem cells on the proliferation and apoptosis gene expression of the retinal pigmented epithelium. Exp Eye Res. 2021;205:108528. doi:10.1016/j.exer.2021.108528.
   PubMed Web of Science ®Google Scholar
• Kannan R, Sreekumar PG, Hinton DR. Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration. Biochim Biophys Acta. 2016;1860(1 Pt B):258–268. doi:10.1016/j.bbagen.2015.05.016.
   PubMed Web of Science ®Google Scholar
• Li S-F, Han Y, Wang F, Su Y. Progress in exosomes and their potential use in ocular diseases. Int J Ophthalmol. 2020;13(9):1493–1498. doi:10.18240/ijo.2020.09.23.
   PubMed Web of Science ®Google Scholar
• Wang Y, Zhang Q, Yang G, Wei Y, Li M, Du E, Li H, Song Z, Tao Y. RPE-derived exosomes rescue the photoreceptors during retina degeneration: an intraocular approach to deliver exosomes into the subretinal space. Drug Deliv. 2021;28(1):218–228. doi:10.1080/10717544.2020.1870584.
   PubMed Web of Science ®Google Scholar
• Sherwood NM, Krueckl SL, McRory JE. The origin and function of the pituitary adenylate cyclase-activating polypeptide (pacap)/glucagon superfamily. Endocr Rev. 2000;21(6):619–670. doi:10.1210/edrv.21.6.0414.
   PubMed Web of Science ®Google Scholar
• Ye D, Shi Y, Xu Y, Huang J. Pacap attenuates optic nerve crush-induced retinal ganglion cell apoptosis via activation of the CREB-Bcl-2 pathway. J Mol Neurosci. 2019;68(3):475–484. doi:10.1007/s12031-019-01309-9.
   PubMed Web of Science ®Google Scholar
• Wang T, Li Y, Guo M, Dong X, Liao M, Du M, Wang X, Yin H, Yan H. Exosome-mediated delivery of the neuroprotective peptide PACAP38 promotes retinal ganglion cell survival and axon regeneration in rats with traumatic optic neuropathy. Front Cell Dev Biol. 2021;9:659783. doi:10.3389/fcell.2021.659783.
   PubMed Web of Science ®Google Scholar