Bone Marrow-Derived Mononuclear Cell Transplants Decrease Retinal Gliosis in Two Animal Models of Inherited Photoreceptor Degeneration

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Oct 3

PMID 33008136

Citations 9

Authors

Johnny Di Pierdomenico

Diego Garcia-Ayuso

Maria Elena Rodriguez Gonzalez-Herrero

David Garcia-Bernal

Miguel Blanquer

Jose Manuel Bernal-Garro

Ana M Garcia-Hernandez

Manuel Vidal-Sanz

Maria P Villegas-Perez

Affiliations

Soon will be listed here.

Abstract

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 Müller 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 2-3-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.

Citing Articles

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina.

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References

Wang X, Shu Q, Ni Y, Xu G . CRISPR-mediated SOX9 knockout inhibits GFAP expression in retinal glial (Müller) cells. Neuroreport. 2018; 29(17):1504-1508. DOI: 10.1097/WNR.0000000000001143. View

Mitchell P, Liew G, Gopinath B, Wong T . Age-related macular degeneration. Lancet. 2018; 392(10153):1147-1159. DOI: 10.1016/S0140-6736(18)31550-2. View

Di Pierdomenico J, Garcia-Ayuso D, Pinilla I, Cuenca N, Vidal-Sanz M, Agudo-Barriuso M . Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities. Front Neuroanat. 2017; 11:14. PMC: 5337514. DOI: 10.3389/fnana.2017.00014. View

Jones B, Watt C, Marc R . Retinal remodelling. Clin Exp Optom. 2005; 88(5):282-91. DOI: 10.1111/j.1444-0938.2005.tb06712.x. View

Yazdanyar A, Zhang P, Dolf C, Smit-McBride Z, Cary W, Nolta J . Effects of intravitreal injection of human CD34 bone marrow stem cells in a murine model of diabetic retinopathy. Exp Eye Res. 2019; 190:107865. PMC: 6957710. DOI: 10.1016/j.exer.2019.107865. View

Assawachananont J, Mandai M, Okamoto S, Yamada C, Eiraku M, Yonemura S . Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice. Stem Cell Reports. 2014; 2(5):662-74. PMC: 4050483. DOI: 10.1016/j.stemcr.2014.03.011. View

Zhu X, Wolff D, Zhang K, He W, Sun X, Lu Y . Molecular Inflammation in the Contralateral Eye After Cataract Surgery in the First Eye. Invest Ophthalmol Vis Sci. 2015; 56(9):5566-73. DOI: 10.1167/iovs.15-16531. View

Maeda A, Mandai M, Takahashi M . Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases. Annu Rev Genomics Hum Genet. 2019; 20:201-216. DOI: 10.1146/annurev-genom-083118-015043. View

Vidal-Villegas B, Di Pierdomenico J, Miralles de Imperial-Ollero J, Ortin-Martinez A, Nadal-Nicolas F, Bernal-Garro J . MelanopsinRGCs Are fully Resistant to NMDA-Induced Excitotoxicity. Int J Mol Sci. 2019; 20(12). PMC: 6627747. DOI: 10.3390/ijms20123012. View

10.

Jiang C, Klassen H, Zhang X, Young M . Laser injury promotes migration and integration of retinal progenitor cells into host retina. Mol Vis. 2010; 16:983-90. PMC: 2890578. View

11.

Li N, Li X, Yuan J . Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia/reperfusion. Graefes Arch Clin Exp Ophthalmol. 2008; 247(4):503-14. DOI: 10.1007/s00417-008-1009-y. View

12.

Otani A, Dorrell M, Kinder K, Moreno S, Nusinowitz S, Banin E . Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest. 2004; 114(6):765-74. PMC: 516263. DOI: 10.1172/JCI21686. View

13.

Siqueira R, Messias A, Voltarelli J, Scott I, Jorge R . Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. Retina. 2011; 31(6):1207-14. DOI: 10.1097/IAE.0b013e3181f9c242. View

14.

Armstrong R, Mousavi M . Overview of Risk Factors for Age-Related Macular Degeneration (AMD). J Stem Cells. 2016; 10(3):171-91. View

15.

Valiente-Soriano F, Salinas-Navarro M, Di Pierdomenico J, Garcia-Ayuso D, Lucas-Ruiz F, Pinilla I . Tracing the retina to analyze the integrity and phagocytic capacity of the retinal pigment epithelium. Sci Rep. 2020; 10(1):7273. PMC: 7190639. DOI: 10.1038/s41598-020-64131-z. View

16.

Qu L, Gao L, Xu H, Duan P, Zeng Y, Liu Y . Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats. Sci Rep. 2017; 7(1):199. PMC: 5428026. DOI: 10.1038/s41598-017-00241-5. View

17.

Warwick A, Lotery A . Genetics and genetic testing for age-related macular degeneration. Eye (Lond). 2017; 32(5):849-857. PMC: 5944647. DOI: 10.1038/eye.2017.245. View

18.

Kondo Y, Ogawa N, Asanuma M, Nishibayashi S, Iwata E, Mori A . Cyclosporin A prevents ischemia-induced reduction of muscarinic acetylcholine receptors with suppression of microglial activation in gerbil hippocampus. Neurosci Res. 1995; 22(1):123-7. DOI: 10.1016/0168-0102(95)00878-w. View

19.

Fritsche L, Igl W, Cooke Bailey J, Grassmann F, Sengupta S, Bragg-Gresham J . A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2015; 48(2):134-43. PMC: 4745342. DOI: 10.1038/ng.3448. View

20.

Wang S, Lu B, Girman S, Duan J, McFarland T, Zhang Q . Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology. PLoS One. 2010; 5(2):e9200. PMC: 2821411. DOI: 10.1371/journal.pone.0009200. View