Analysis of the results of transplantation of the retinal pigment epithelium in the experiment

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: A promising method for treating the pathology of the retinal pigment epithelium in age-related macular degeneration is cell replacement therapy.

AIM: The aim of the study was to analyze the results of cell transplantation in the form of a cell suspension into the subretinal space at various times.

MATERIALS AND METHODS: The material of the study was 20 rabbits (40 eyes) of the New Zealand albino breed. A month after the modeling of retinal pigment epithelium atrophy and retinal degeneration, rabbits underwent subretinal transplantation of induced retinal pigment epithelium in the form of a cell suspension. Optical coherence tomography and autofluorescence studies were conducted in a period of up to 8 months. Enucleated eyes of animals were subjected to morphological study.

RESULTS: When observing rabbits with a previously created model of atrophy in the long term, it was found that the cells of the transplanted retinal pigment epithelium remained viable for the entire period. There were no inflammatory reactions from the eyeball, clouding of the optical media, pathological changes in the structure of the retina.

CONCLUSION: Thus, with the introduction of a suspension of induced retinal pigment epithelium cells with atrophy of the retinal pigment epithelium, the injected cells retain their viability for up to 8 months.

Full Text

Restricted Access

About the authors

Maria A. Lagarkova

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: lagar@rcpcm.org
ORCID iD: 0000-0001-9594-1134
SPIN-code: 4315-1701

Dr. Sci. (Biol.), Associate Member of Russian Academy of Sciences

Russian Federation, Moscow

Lyudmila A. Katargina

The Helmholtz Moscow Research Institute of Eye Diseases

Email: katargina@igb.ru
ORCID iD: 0000-0002-4857-0374

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Natalya S. Izmailova

The Helmholtz Moscow Research Institute of Eye Diseases

Email: nizm2013@mail.ru
ORCID iD: 0000-0002-4713-5661
SPIN-code: 1984-1519

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Pavel A. Ilyukhin

The Helmholtz Moscow Research Institute of Eye Diseases

Email: paulilukhin@gmail.com
ORCID iD: 0000-0001-9552-6782
SPIN-code: 2407-5436

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Anatoliy E. Kharitonov

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: kharitonov.ae@rcpcm.org
ORCID iD: 0000-0003-1420-1164
SPIN-code: 9585-9205
Russian Federation, Moscow

Olga A. Utkina

The Helmholtz Moscow Research Institute of Eye Diseases

Author for correspondence.
Email: olga_utkina17@mail.ru
ORCID iD: 0000-0001-8463-6337
SPIN-code: 2465-0604

PhD, Student

Russian Federation, Moscow

Natalia V. Neroeva

The Helmholtz Moscow Research Institute of Eye Diseases

Email: nneroeva@gmail.com
ORCID iD: 0000-0003-1038-2746
SPIN-code: 7621-9577

Cand. Sci. (Med.)

Russian Federation, Moscow

References

  1. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106–116. doi: 10.1016/S2214-109X(13)70145-1
  2. Cabral de Guimaraes TA, Daich Varela M, Georgiou M, Michaelides M. Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions. Br J Ophthalmol. 2022;106(3):297–304. doi: 10.1136/bjophthalmol-2020-318452
  3. Duarri A, Rodríguez-Bocanegra E, Martínez-Navarrete G, et al. Transplantation of human induced pluripotent stem cell-derived retinal pigment epithelium in a swine model of geographic atrophy. Int J Mol Sci. 2021;22(19):10497. doi: 10.3390/ijms221910497
  4. Group CR, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20):1897–1908. doi: 10.1056/NEJMoa1102673
  5. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (vegf trap-eye) in wet agerelated macular degeneration. Ophthalmology. 2012;119(12):2537–2548. doi: 10.1016/j.ophtha.2012.09.006
  6. Sheremet NL, Mikaelyan AA, Andreev AYu, Kiselev SL. Possibilities of treating retinal diseases in patients with damaged retinal pigment epithelium. Vestnik Oftalmologii. 2019;135(5):226–234. (In Russ). doi: 10.17116/oftalma2019135052226
  7. Gayduk KY, Churashov SV, Kulikov AN. Stem cell-based technologies in treatment of age-related macular degeneration patients: current state of the problem. Ophthalmology Reports. 2019;12(4): 35–41. (In Russ). doi: 10.17816/OV12604
  8. Hacenko EI. Tehnologija podgotovki i transplantacii 3D kletochnyh sferoidov retinal’nogo pigmentnogo jepitelija v jeksperimente [dissertation]. Мoscow, 2019. Available from: https://www.dissercat.com/content/tekhnologiya-podgotovki-i-transplantatsii-3d-kletochnykh-sferoidov-retinalnogo-pigmentnogo (In Russ).
  9. Kashani AH. Stem cell therapy in non-neovascular age-related macular degeneration stem cell therapy in non-neovascular AMD. Invest Ophthalmol Vis Sci. 2016;57(5):ORSFm1–ORSFm 9. doi: 10.1167/iovs.15-17681
  10. O’Neill HC, Limnios IJ, Barnett NL. Advancing a stem cell therapy for age-related macular degeneration. Curr Stem Cell Res Ther. 2020;15(2):89–97. doi: 10.2174/1574888X15666191218094020
  11. Nazari H, Zhang L, Zhu D, et al. Stem cell based therapies for age-related macular degeneration: the promises and the challenges. Prog Retin Eye Res. 2015;48:1–39. doi: 10.1016/j.preteyeres.2015.06.004
  12. Vitillo L, Tovell VE, Coffey P. Treatment of age-related macular degeneration with pluripotent stem cell-derived retinal pigment epithelium. Curr Eye Res. 2020;45(3):361–371. doi: 10.1080/02713683.2019.1691237
  13. Humayun MS, Weiland J, Fujii GY, et al. Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vis Res. 2003;43(24):2573–2581. doi: 10.1016/s0042-6989(03)00457-7
  14. Maximov VV, Lagarkova MA, Kiselev SL. Gene and cell therapy of retinal diseases. Genes & Cells. 2012;7(3):12–20. (In Russ). doi: 10.23868/gc121564
  15. Borooah S, Phillips M, Bilican B, et al. Using human induced pluripotent stem cells to treat retinal disease. Prog Retin Eye Res. 2013;37:163–181. doi: 10.1016/j.preteyeres.2013.09.002
  16. Sheremet NL, Mikaelyan AA, Andreev AYu, Kiselev SL. Possibilities of treating retinal diseases in patients with damaged retinal pigment epithelium. Vestnik Oftalmologii. 2019;135(5):226–234. (In Russ). doi: 10.17116/oftalma2019135052226
  17. Mandai M, Watanabe A, Kurimoto Y, et al. autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med. 2017;376(11):1038–1046. doi: 10.1056/NEJMoa1608368
  18. Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pig-ment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. 2015;385(9967):509–516. doi: 10.1016/S0140-6736(14)61376-3
  19. Song WK, Park K-M, Kim H-J, et al. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in asian patients. Stem Cell Rep. 2015;4(5):860–872. doi: 10.1016/j.stemcr.2015.04.005
  20. Falkner-Radler CI, Krebs I, Glittenberg C, et al. Human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study. Br J Ophthalmol. 2011;95(3):370–375. doi: 10.1136/bjo.2009.176305
  21. Mehat MS, Sundaram V, Ripamonti C, et al. Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells in macular degeneration. Ophthalmology. 2018;125(11):1765–1775. doi: 10.1016/j.ophtha.2018.04.037
  22. Schwartz SD, Hubschman J-P, Heilwell G, et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379(9817):713–720. doi: 10.1016/S0140-6736(12)60028-2
  23. Diniz B, Thomas P, Thomas B, et al. Subretinal implantation of retinal pigment epithelial cells derived from human embryonic stem cells: improved survival when implanted as a monolayer. Invest Ophthalmol Vis Sci. 2013;54(7):5087–5096. doi: 10.1167/iovs.12-11239
  24. Koster C, Wever KE, Wagstaff PE, et al. A systematic review on transplantation studies of the retinal pigment epithelium in animal models. Int J Mol Sci. 2020;21(8):2719. doi: 10.3390/ijms21082719
  25. Patent RUS N 2709247/17.12.2019. Neroev VV, Katargina LA, Neroeva NV, et al. Sposob modelirovanija atrofii retinal’nogo pigmentnogo jepitelija. Available from: https://eyepress.ru/article.aspx?42226 (In Russ).
  26. Neroeva NV, Neroev VV, Katargina LA, et al. Experimental stem cell replacement transplantation in retinal pigment epithelium atrophy. Vestnik Oftalmologii. 2022;138(3):7–15. (In Russ). doi: 10.17116/oftalma20221380317
  27. Patent RUS N 2729937/13.08.2020. Bjul. N 23. Neroeva NV, Neroev VV, Katargina LA, et al. Sposob subretinal’noj transplantacii kletok retinal’nogo pigmentnogo jepitelija (RPJe), differencirovannyh iz inducirovannyh pljuripotentnyh stvolovyh kletok cheloveka pri atrofii retinal’nogo pigmentnogo jepitelija v jeksperimente. Available from: https://www.mediasphera.ru/issues/vestnik-oftalmologii/2022/3/10042465X2022031007 (In Russ).

Supplementary files

Supplementary Files
Action
1. Fig. 1. Condition of the rabbit retina with a model of pigment epithelium atrophy before transplantation of iPSC-RPE cell suspension: a — OCT image of the retina in the en face mode (green line indicates a cross section of the scan); b — transverse OCT scan of the retina; c — fundus autofluorescence.

Download (524KB)
Indexing metadata
2. Fig. 2. Damage zone of the rabbit’s own RPE on the 14th day of bevacizumab administration: a — ×400; b — ×630; c — own RPE without signs of damage (×630). Combined staining: nuclei — Harris hematoxylin, cell membranes — silver impregnation.

Download (521KB)
Indexing metadata
3. Fig. 3. The area of damage to the rabbit's own RPE on the 14th day of the introduction of bevacizumab. Cross section of the retina and choroid, stained with hematoxylin and eosin; ×200.

Download (418KB)
Indexing metadata
4. Fig. 4. State of the retina 2 weeks after iPSC-RPE cell suspension transplantation: a — OCT image of the retina in the en face mode (green line indicates a cross section of the scan); b — transverse OCT scan of the retina; c — fundus autofluorescence.

Download (712KB)
Indexing metadata
5. Fig. 5. Planar preparation of the choroid and RPE with implanted iPSC-RPE in the form of a monolayer on the 14th day of administration of the iPSC-RPE suspension. Combined staining: nuclei — Harris hematoxylin, cell membranes — silver impregnation; ×400 (in the inset — ×630).

Download (347KB)
Indexing metadata
6. Fig. 6. Preparation of the retinal zone on the 14th day after the administration of the iPSC-RPE suspension: iPSC-RPE cells (1) have the form of a monolayer; retina (2); choroid (3); cross section staining — hematoxylin and eosin; ×200 (in the inset — ×630).

Download (419KB)
Indexing metadata
7. Fig. 7. State of the retina 3 months after transplantation of iPSC-RPE cell suspension: а — fundus autofluorescence; b — OCT image of the retina in the en face mode (green line indicates a cross section of the scan); c — transverse OCT scan of the retina.

Download (505KB)
Indexing metadata
8. Fig. 8. Planar preparation of choroid and RPE with implanted iPSCs-RPE in the form of a monolayer at 4 months after administration of iPSC-RPE suspension. Combined staining: nuclei — Harris hematoxylin, cell membranes — silver impregnation; magnification ×630. In the inset, the same preparation, oil immersion, ×1000, the focus is shifted to the apical surface of the cell.

Download (430KB)
Indexing metadata

Copyright (c) 2023 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 85657 от 21.07.2023 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies