EXPERIMENTAL RATIONALE OF THE USE OF CELL THERAPY FOR THE TREATMENT OF GLAUCOMA OPTICAL NEUROPATHY

Keywords: glaucoma, multipotent stem cells, cell therapy

Abstract

Development of new effective treatments for glaucomatous optic neuropathy is one of the most acute aspects of modern ophthalmology.

The aim of the work is to investigate the effectiveness of cell therapy with postnatal multipotent neural crest stem cells (NCSCs) using different cell delivery methods in a model of adrenaline-induced glaucoma.

Materials and methods. Glaucoma was induced in Wistar rats by intraperitoneal injections of 10 μg to 15 μg/100 g body weight of 0.18 % adrenaline hydrotartrate. NCSCs were delivered intravenously (5 million cells), retrobulbarly (0.5 million cells) or parabulbarly (0.5 million cells). Histomorphometric analysis of the retina was performed on stained haematoxylin-eosin sections with a thickness of 5 μm one month after the delivery of NCSCs.

Results. NCSCs transplantation by all modes of delivery caused positive morphological changes to varying degrees. Intravenous administration induced a decrease in edema in all retinal layers and a slight restoration of the cytoarchitectonics of the retinal layers. The parabulbar administration of NCSCs led to a decrease in edema and the restoration of the cytoarchitectonics of the layers, most pronouncedly the ganglion cell layer and the inner retinal layer. After the retrobulbar administration of NCSCs, the reduction in edema and restoration of the cytoarchitectonics of the layers were the most pronounced.

Conclusions. According to the results of the study, the positive effect of NCSCs transplantation in an experimental model of glaucoma was the most pronounced following the retrobulbar injection of cells. Further investigations of the mechanisms of the effect of transplanted NCSCs on retinal structure restoration are needed.

Downloads

Download data is not yet available.

Author Biographies

Sergiy Rykov, Shupyk National Medical Academy of Postgraduate Education

Department of Ophthalmology

Oksana Petrenko, Shupyk National Medical Academy of Postgraduate Education

Department of Ophthalmology

Antonina Yakovets, Shupyk National Medical Academy of Postgraduate Education

Department of Ophthalmology

Dmytro Zubov, State Institute of Genetic and Regenerative Medicine NAMS of Ukraine

Department of Genetic Diagnostics

Roman Vasyliev, State Institute of Genetic and Regenerative Medicine NAMS of Ukraine

Department of Genetic Diagnostics

References

Weinreb, R. N., Aung, T., Medeiros, F. A. (2014). The Pathophysiology and Treatment of Glaucoma. JAMA, 311(18), 1901–1911. doi: http://doi.org/10.1001/jama.2014.3192

Wang, X., Harmon, J., Zabrieskie, N., Chen, Y., Grob, S., Williams, B. et. al. (2010). Using the Utah Population Database to assess familial risk of primary open angle glaucoma. Vision Research, 50 (23), 2391–2395. doi: http://doi.org/10.1016/j.visres.2010.09.018

Tham, Y.-C., Li, X., Wong, T. Y., Quigley, H. A., Aung, T., Cheng, C.-Y. (2014). Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040. Ophthalmology, 121 (11), 2081–2090. doi: http://doi.org/10.1016/j.ophtha.2014.05.013

Križaj D. (2019). What is glaucoma? Webvision: The Organization of the Retina and Visual System. Available at: https://webvision.med.utah.edu/book/part-xii-cell-biology-of-retinal-degenerations/what-is-glaucoma/

Mahabadi N., Foris L.A., Tripathy K. (2019). Open Angle Glaucoma. Available at: http://www.ncbi.nlm.nih.gov/pubmed/28722917

Wang, Y., Xu, K., Zhang, H., Zhao, J., Zhu, X., Wang, Y., Wu, R. (2014). Retinal ganglion cell death is triggered by paraptosis via reactive oxygen species production: A brief literature review presenting a novel hypothesis in glaucoma pathology. Molecular Medicine Reports, 10 (3), 1179–1183. doi: http://doi.org/10.3892/mmr.2014.2346

Elisseeff, J., Guo, Q., Lu, Q., Madrid, M., Chae, Jj. (2013). Future perspectives for regenerative medicine in ophthalmology. Middle East African Journal of Ophthalmology, 20 (1), 38–45. doi: http://doi.org/10.4103/0974-9233.106385

Manuguerra-GagnÉ, R., Boulos, P. R., Ammar, A., Leblond, F. A., Krosl, G., Pichette, V. et. al. (2013). Transplantation of Mesenchymal Stem Cells Promotes Tissue Regeneration in a Glaucoma Model Through Laser-Induced Paracrine Factor Secretion and Progenitor Cell Recruitment. STEM CELLS, 31 (6), 1136–1148. doi: http://doi.org/10.1002/stem.1364

Roubeix, C., Godefroy, D., Mias, C., Sapienza, A., Riancho, L., Degardin, J. et. al. (2015). Intraocular pressure reduction and neuroprotection conferred by bone marrow-derived mesenchymal stem cells in an animal model of glaucoma. Stem Cell Research & Therapy, 6 (1). doi: http://doi.org/10.1186/s13287-015-0168-0

Mead, B., Hill, L. J., Blanch, R. J., Ward, K., Logan, A., Berry, M. et. al. (2016). Mesenchymal stromal cell–mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma. Cytotherapy, 18 (4), 487–496. doi: http://doi.org/10.1016/j.jcyt.2015.12.002

Weber, M., Apostolova, G., Widera, D., Mittelbronn, M., Dechant, G., Kaltschmidt, B., Rohrer, H. (2015). Alternative Generation of CNS Neural Stem Cells and PNS Derivatives from Neural Crest-Derived Peripheral Stem Cells. Stem Cells, 33 (2), 574–588. doi: http://doi.org/10.1002/stem.1880

Narytnyk, A., Verdon, B., Loughney, A., Sweeney, M., Clewes, O., Taggart, M. J., Sieber-Blum, M. (2014). Differentiation of Human Epidermal Neural Crest Stem Cells (hEPI-NCSC) into Virtually Homogenous Populations of Dopaminergic Neurons. Stem Cell Reviews and Reports, 10 (2), 316–326. doi: http://doi.org/10.1007/s12015-013-9493-9

Binder, E., Rukavina, M., Hassani, H., Weber, M., Nakatani, H., Reiff, T. et. al. (2011). Peripheral Nervous System Progenitors Can Be Reprogrammed to Produce Myelinating Oligodendrocytes and Repair Brain Lesions. Journal of Neuroscience, 31 (17), 6379–6391. doi: http://doi.org/10.1523/jneurosci.0129-11.2011

Liu, J. A., Cheung, M. (2016). Neural crest stem cells and their potential therapeutic applications. Developmental Biology, 419 (2), 199–216. doi: http://doi.org/10.1016/j.ydbio.2016.09.006

Mikheytseva, I. N. (2014). Glaucoma modeling and adrenal stress. The Journal of Clinical and Experimental Medical Research, 2 (4), 427–437. Available at: http://essuir.sumdu.edu.ua/handle/123456789/38944

Vasyliev, R. G. (2014). In vitro properties of neural crest-derived multipotent stem cells from a bulge region of whisker follicle. Biotechnologia Acta, 7 (4), 71–79. doi: http://doi.org/10.15407/biotech7.04.071

Vasyliev, R. G., Gubar, O. S., Gordiienko, I. M., Litvinova, L. S., Rodnichenko, A. E., Shupletsova, V. V. et.al. (2019). Comparative Analysis of Biological Properties of Large-Scale Expanded Adult Neural Crest-Derived Stem Cells Isolated from Human Hair Follicle and Skin Dermis. Stem Cells International, 2019, 1–20. doi: http://doi.org/10.1155/2019/9640790

Ding, S., Kumar, S., Mok, P. (2017). Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases. International Journal of Molecular Sciences, 18 (8), 1406. doi: http://doi.org/10.3390/ijms18081406

Dang, Y., Zhang, C., Zhu, Y. (2015). Stem cell therapies for age-related macular degeneration: the past, present, and future. Clinical Interventions in Aging, 10, 255–264. doi: http://doi.org/10.2147/cia.s73705

Johnson, T. V., Bull, N. D., Hunt, D. P., Marina, N., Tomarev, S. I., Martin, K. R. (2010). Neuroprotective Effects of Intravitreal Mesenchymal Stem Cell Transplantation in Experimental Glaucoma. Investigative Opthalmology & Visual Science, 51 (4), 2051–2059. doi: http://doi.org/10.1167/iovs.09-4509


👁 371
⬇ 316
Published
2020-03-31
How to Cite
Rykov, S., Petrenko, O., Yakovets, A., Zubov, D., & Vasyliev, R. (2020). EXPERIMENTAL RATIONALE OF THE USE OF CELL THERAPY FOR THE TREATMENT OF GLAUCOMA OPTICAL NEUROPATHY. EUREKA: Health Sciences, (2), 40-46. https://doi.org/10.21303/2504-5679.2020.001187
Section
Medicine and Dentistry