{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T16:09:48Z","timestamp":1773245388764,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Lucha contra la Ceguera","award":["FUNDALUCE"],"award-info":[{"award-number":["FUNDALUCE"]}]},{"name":"Fundaci\u00f3n S\u00e9neca, Agencia de Ciencia y Tecnolog\u00eda Regi\u00f3n de Murcia","award":["19881\/GERM\/15"],"award-info":[{"award-number":["19881\/GERM\/15"]}]},{"name":"Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional \u201cUna Manera de Hacer Europa\u201d","award":["SAF2015-67643-P"],"award-info":[{"award-number":["SAF2015-67643-P"]}]},{"name":"Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional \u201cUna Manera de Hacer Europa\u201d","award":["PI19\/00203"],"award-info":[{"award-number":["PI19\/00203"]}]},{"name":"Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional \u201cUna Manera de Hacer Europa\u201d","award":["RD16\/0008\/0026"],"award-info":[{"award-number":["RD16\/0008\/0026"]}]},{"name":"Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional \u201cUna Manera de Hacer Europa\u201d","award":["RED2018-102499-T"],"award-info":[{"award-number":["RED2018-102499-T"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inherited photoreceptor degenerations are not treatable diseases and a frequent cause of blindness in working ages. In this study we investigate the safety, integration and possible rescue effects of intravitreal and subretinal transplantation of adult human bone-marrow-derived mononuclear stem cells (hBM-MSCs) in two animal models of inherited photoreceptor degeneration, the P23H-1 and the Royal College of Surgeons (RCS) rat. Immunosuppression was started one day before the injection and continued through the study. The hBM-MSCs were injected in the left eyes and the animals were processed 7, 15, 30 or 60 days later. The retinas were cross-sectioned, and L- and S- cones, microglia, astrocytes and M\u00fcller cells were immunodetected. Transplantations had no local adverse effects and the CD45+ cells remained for up to 15 days forming clusters in the vitreous and\/or a 2\u20133-cells-thick layer in the subretinal space after intravitreal or subretinal injections, respectively. We did not observe increased photoreceptor survival nor decreased microglial cell numbers in the injected left eyes. However, the injected eyes showed decreased GFAP immunoreactivity. We conclude that intravitreal or subretinal injection of hBM-MSCs in dystrophic P23H-1 and RCS rats causes a decrease in retinal gliosis but does not have photoreceptor neuroprotective effects, at least in the short term. However, this treatment may have a potential therapeutic effect that merits further investigation.<\/jats:p>","DOI":"10.3390\/ijms21197252","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T09:04:12Z","timestamp":1601543052000},"page":"7252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Bone Marrow-Derived Mononuclear Cell Transplants Decrease Retinal Gliosis in Two Animal Models of Inherited Photoreceptor Degeneration"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9124-9247","authenticated-orcid":false,"given":"Johnny","family":"Di Pierdomenico","sequence":"first","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, 30120 Murcia, Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7639-5366","authenticated-orcid":false,"given":"Diego","family":"Garc\u00eda-Ayuso","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, 30120 Murcia, Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Elena Rodr\u00edguez","family":"Gonz\u00e1lez-Herrero","sequence":"additional","affiliation":[{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"},{"name":"Servicio de Oftalmolog\u00eda, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, Carretera Madrid-Cartagena s\/n, 30120 El Palmar Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6610-8442","authenticated-orcid":false,"given":"David","family":"Garc\u00eda-Bernal","sequence":"additional","affiliation":[{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"},{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, Carretera Madrid-Cartagena s\/n, 30120 El Palmar Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Blanquer","sequence":"additional","affiliation":[{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"},{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, Carretera Madrid-Cartagena s\/n, 30120 El Palmar Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Manuel","family":"Bernal-Garro","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, 30120 Murcia, Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M.","family":"Garc\u00eda-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"},{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, Carretera Madrid-Cartagena s\/n, 30120 El Palmar Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-1615","authenticated-orcid":false,"given":"Manuel","family":"Vidal-Sanz","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, 30120 Murcia, Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-482X","authenticated-orcid":false,"given":"Mar\u00eda P.","family":"Villegas-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, 30120 Murcia, Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2013.12.004","article-title":"Nature and nurture-genes and environment-predict onset and progression of macular degeneration","volume":"40","author":"Sobrin","year":"2014","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_2","first-page":"171","article-title":"Overview of Risk Factors for Age-Related Macular Degeneration (AMD)","volume":"10","author":"Armstrong","year":"2015","journal-title":"J. Stem Cells"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/eye.2017.245","article-title":"Genetics and genetic testing for age-related macular degeneration","volume":"32","author":"Warwick","year":"2018","journal-title":"Eye"},{"key":"ref_4","first-page":"844","article-title":"Global data on visual impairment in the year 2002","volume":"82","author":"Resnikoff","year":"2004","journal-title":"Bull. World Health Organ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1221","DOI":"10.1016\/S2214-109X(17)30393-5","article-title":"Global causes of blindness and distance vision impairment 1990-2020: A systematic review and meta-analysis","volume":"5","author":"Flaxman","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/bjophthalmol-2017-311258","article-title":"Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe in 2015: Magnitude, temporal trends and projections","volume":"102","author":"Bourne","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1167\/iovs.06-0440","article-title":"Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant retinitis pigmentosa","volume":"47","author":"Sullivan","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.preteyeres.2017.10.004","article-title":"Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives","volume":"63","author":"Dias","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2017.01.004","article-title":"Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases","volume":"58","author":"Jones","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev-vision-091517-034425","article-title":"Microglia in the Retina: Roles in Development, Maturity, and Disease","volume":"4","author":"Silverman","year":"2018","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1167\/iovs.08-3004","article-title":"Cone-rod dependence in the rat retina: Variation with the rate of rod damage","volume":"50","author":"Chrysostomou","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/aos.13141","article-title":"A review of the mechanisms of cone degeneration in retinitis pigmentosa","volume":"94","author":"Narayan","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.preteyeres.2017.08.004","article-title":"The mechanism of cone cell death in Retinitis Pigmentosa","volume":"62","author":"Campochiaro","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.4103\/1673-5374.251204","article-title":"Role of microglial cells in photoreceptor degeneration","volume":"14","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","article-title":"Age-related macular degeneration","volume":"392","author":"Mitchell","year":"2018","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.exer.2010.10.003","article-title":"Retinal ganglion cell numbers and delayed retinal ganglion cell death in the P23H rat retina","volume":"91","author":"Agudo","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_20","first-page":"1716","article-title":"Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration","volume":"17","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1136\/bjophthalmol-2013-303958","article-title":"Sectorial loss of retinal ganglion cells in inherited photoreceptor degeneration is due to RGC death","volume":"98","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.4103\/1673-5374.239436","article-title":"Retinal remodeling following photoreceptor degeneration causes retinal ganglion cell death","volume":"13","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Garcia-Ayuso, D., Di Pierdomenico, J., Vidal-Sanz, M., and Villegas-Perez, M.P. (2019). Retinal Ganglion Cell Death as a Late Remodeling Effect of Photoreceptor Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184649"},{"key":"ref_24","first-page":"14","article-title":"Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities","volume":"11","author":"Pinilla","year":"2017","journal-title":"Front. Neuroanat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S1350-9462(03)00039-9","article-title":"Neural remodeling in retinal degeneration","volume":"22","author":"Marc","year":"2003","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1444-0938.2005.tb06712.x","article-title":"Retinal remodelling","volume":"88","author":"Jones","year":"2005","journal-title":"Clin. Exp. Optom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100771","DOI":"10.1016\/j.preteyeres.2019.07.004","article-title":"Persistent remodeling and neurodegeneration in late-stage retinal degeneration","volume":"74","author":"Pfeiffer","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.preteyeres.2015.01.003","article-title":"Cellular strategies for retinal repair by photoreceptor replacement","volume":"46","author":"Jayakody","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2019.03.001","article-title":"Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach","volume":"71","author":"Gagliardi","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2018.11.001","article-title":"Transplantation of photoreceptors into the degenerative retina: Current state and future perspectives","volume":"69","author":"Gasparini","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100779","DOI":"10.1016\/j.preteyeres.2019.100779","article-title":"Retinal stem cell transplantation: Balancing safety and potential","volume":"75","author":"Singh","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1038\/s41598-018-20171-0","article-title":"Cone degeneration is triggered by the absence of USH1 proteins but prevented by antioxidant treatments","volume":"8","author":"Trouillet","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.preteyeres.2018.11.003","article-title":"Stemming retinal regeneration with pluripotent stem cells","volume":"69","author":"Jin","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev-genom-083118-015043","article-title":"Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases","volume":"20","author":"Maeda","year":"2019","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_35","first-page":"983","article-title":"Laser injury promotes migration and integration of retinal progenitor cells into host retina","volume":"16","author":"Jiang","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.stemcr.2014.03.011","article-title":"Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice","volume":"2","author":"Assawachananont","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1038\/s41598-020-61167-z","article-title":"A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential","volume":"10","author":"Petrenko","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/978-1-59745-060-7_18","article-title":"Bone marrow-derived mesenchymal stem cells: Isolation, expansion, characterization, viral transduction, and production of conditioned medium","volume":"482","author":"Gnecchi","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.exer.2010.06.024","article-title":"Human adult bone marrow-derived somatic cells rescue vision in a rodent model of retinal degeneration","volume":"91","author":"Lu","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1634\/stemcells.20-4-279","article-title":"Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina","volume":"20","author":"Tomita","year":"2002","journal-title":"Stem Cells"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s00417-008-1009-y","article-title":"Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia\/reperfusion","volume":"247","author":"Li","year":"2009","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol. Albrecht Von Graefes Arch. Fur Klin. Und Exp. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.brainres.2014.08.070","article-title":"Sustained effect of bone marrow mononuclear cell therapy in axonal regeneration in a model of optic nerve crush","volume":"1587","author":"Gubert","year":"2014","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.preteyeres.2016.10.002","article-title":"Advances in bone marrow stem cell therapy for retinal dysfunction","volume":"56","author":"Park","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107865","DOI":"10.1016\/j.exer.2019.107865","article-title":"Effects of intravitreal injection of human CD34(+) bone marrow stem cells in a murine model of diabetic retinopathy","volume":"190","author":"Yazdanyar","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1172\/JCI200421686","article-title":"Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells","volume":"114","author":"Otani","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.exer.2013.10.023","article-title":"Transplantation of human bone marrow mesenchymal stem cells as a thin subretinal layer ameliorates retinal degeneration in a rat model of retinal dystrophy","volume":"118","author":"Tzameret","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.scr.2015.08.007","article-title":"Epiretinal transplantation of human bone marrow mesenchymal stem cells rescues retinal and vision function in a rat model of retinal degeneration","volume":"15","author":"Tzameret","year":"2015","journal-title":"Stem Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1167\/iovs.16-19252","article-title":"Intravitreal Administration of Human Bone Marrow CD34+ Stem Cells in a Murine Model of Retinal Degeneration","volume":"57","author":"Moisseiev","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","first-page":"474","article-title":"CD34-positive stem cells: In the treatment of heart and vascular disease in human beings","volume":"38","author":"Mackie","year":"2011","journal-title":"Tex. Heart Inst. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/jocs.13789","article-title":"The current status of stem cell therapy in ischemic heart disease","volume":"33","author":"Michler","year":"2018","journal-title":"J. Card. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"960","DOI":"10.2337\/db06-1254","article-title":"Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells","volume":"56","author":"Caballero","year":"2007","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1167\/iovs.11-8833","article-title":"Long-term effects of intravitreal injection of GMP-grade bone-marrow-derived CD34+ cells in NOD-SCID mice with acute ischemia-reperfusion injury","volume":"53","author":"Park","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s00417-006-0382-7","article-title":"Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse","volume":"245","author":"Arnhold","year":"2007","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol. Albrecht Von Graefes Arch. Fur Klin. Und Exp. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, S., Lu, B., Girman, S., Duan, J., McFarland, T., Zhang, Q.S., Grompe, M., Adamus, G., Appukuttan, B., and Lund, R. (2010). Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology. Plos ONE, 5.","DOI":"10.1371\/journal.pone.0009200"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1600-0420.2007.00987.x","article-title":"Intravitreal autologous bone marrow-derived mononuclear cell transplantation: A feasibility report","volume":"86","author":"Jonas","year":"2008","journal-title":"Acta Ophthalmol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1590\/S0004-27492010000500019","article-title":"Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells","volume":"73","author":"Siqueira","year":"2010","journal-title":"Arq. Bras. De Oftalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1097\/IAE.0b013e3181f9c242","article-title":"Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: A phase I trial","volume":"31","author":"Siqueira","year":"2011","journal-title":"Retina"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1167\/iovs.14-15415","article-title":"Intravitreal autologous bone marrow CD34+ cell therapy for ischemic and degenerative retinal disorders: Preliminary phase 1 clinical trial findings","volume":"56","author":"Park","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt\u2019s macular dystrophy: Follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/cne.21279","article-title":"Rat retinal microglial cells under normal conditions, after optic nerve section, and after optic nerve section and intravitreal injection of trophic factors or macrophage inhibitory factor","volume":"501","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/0168-0102(95)00878-W","article-title":"Cyclosporin A prevents ischemia-induced reduction of muscarinic acetylcholine receptors with suppression of microglial activation in gerbil hippocampus","volume":"22","author":"Kondo","year":"1995","journal-title":"Neurosci. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/brain\/awl263","article-title":"The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin A","volume":"130","author":"Sliwa","year":"2007","journal-title":"Brain J. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fncel.2019.00273","article-title":"Combined Cyclosporin A and Hypothermia Treatment Inhibits Activation of BV-2 Microglia but Induces an Inflammatory Response in an Ischemia\/Reperfusion Hippocampal Slice Culture Model","volume":"13","author":"Wowro","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.exer.2017.10.023","article-title":"Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration","volume":"167","author":"LaVail","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41598-017-00241-5","article-title":"Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats","volume":"7","author":"Qu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s12974-014-0186-3","article-title":"Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects","volume":"11","author":"Noailles","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"ref_67","first-page":"2954721","article-title":"Retinal Macroglial Responses in Health and Disease","volume":"2016","author":"Rojas","year":"2016","journal-title":"Biomed Res. Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1634\/stemcells.2005-0507","article-title":"A comparison of neural differentiation and retinal transplantation with bone marrow-derived cells and retinal progenitor cells","volume":"24","author":"Tomita","year":"2006","journal-title":"Stem Cells"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.exer.2007.04.007","article-title":"Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration","volume":"85","author":"Inoue","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3742","DOI":"10.1167\/iovs.08-3314","article-title":"Effects of bone marrow mesenchymal stem cell transplantation on light-damaged retina","volume":"51","author":"Zhang","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1007\/s10792-016-0391-4","article-title":"A comparison of responses to intravitreal bevacizumab, ranibizumab, or aflibercept injections for neovascular age-related macular degeneration","volume":"37","author":"Park","year":"2017","journal-title":"Int. Ophthalmol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1167\/iovs.18-23806","article-title":"Resveratrol Delays Retinal Ganglion Cell Loss and Attenuates Gliosis-Related Inflammation from Ischemia-Reperfusion Injury","volume":"59","author":"Luo","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1097\/WNR.0000000000001143","article-title":"CRISPR-mediated SOX9 knockout inhibits GFAP expression in retinal glial (Muller) cells","volume":"29","author":"Wang","year":"2018","journal-title":"Neuroreport"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4392","DOI":"10.1167\/iovs.18-24621","article-title":"Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration","volume":"59","author":"Scholz","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Lucas-Ruiz, F., Galindo-Romero, C., Rodriguez-Ramirez, K.T., Vidal-Sanz, M., and Agudo-Barriuso, M. (2019). Neuronal Death in the Contralateral Un-Injured Retina after Unilateral Axotomy: Role of Microglial Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225733"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1167\/iovs.12-11207","article-title":"Effect of brain-derived neurotrophic factor on mouse axotomized retinal ganglion cells and phagocytic microglia","volume":"54","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.1167\/iovs.15-16531","article-title":"Molecular Inflammation in the Contralateral Eye After Cataract Surgery in the First Eye","volume":"56","author":"Zhu","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Vidal-Villegas, B., Di Pierdomenico, J., Miralles de Imperial-Ollero, J.A., Ortin-Martinez, A., Nadal-Nicolas, F.M., Bernal-Garro, J.M., Cuenca Navarro, N., Villegas-Perez, M.P., and Vidal-Sanz, M. (2019). Melanopsin(+)RGCs Are fully Resistant to NMDA-Induced Excitotoxicity. Int. J. Mol. Sci., 20.","DOI":"10.20944\/preprints201905.0278.v1"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s12974-017-0982-7","article-title":"Microglial dynamics after axotomy-induced retinal ganglion cell death","volume":"14","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1167\/iovs.61.3.47","article-title":"Coordinated Intervention of Microglial and Muller Cells in Light-Induced Retinal Degeneration","volume":"61","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1002\/stem.2095","article-title":"Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation","volume":"33","author":"Tassoni","year":"2015","journal-title":"Stem Cells"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7273","DOI":"10.1038\/s41598-020-64131-z","article-title":"Tracing the retina to analyze the integrity and phagocytic capacity of the retinal pigment epithelium","volume":"10","author":"Pinilla","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1167\/iovs.07-0992","article-title":"Morphological and functional rescue in RCS rats after RPE cell line transplantation at a later stage of degeneration","volume":"49","author":"Wang","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1167\/iovs.16-19618","article-title":"Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats","volume":"57","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nm0696-649","article-title":"Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy","volume":"2","author":"Bennett","year":"1996","journal-title":"Nat. Med."},{"key":"ref_86","first-page":"52247","article-title":"Performing subretinal injections in rodents to deliver retinal pigment epithelium cells in suspension","volume":"95","author":"Westenskow","year":"2015","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1167\/iovs.17-23258","article-title":"Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration","volume":"59","author":"Marie","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:27Z","timestamp":1760177727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":87,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21197252"],"URL":"https:\/\/doi.org\/10.3390\/ijms21197252","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]}}}