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

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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.

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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

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Supplementary files

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2. 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.

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3. 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.

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4. 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.

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5. 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.

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6. 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).

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7. 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).

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8. 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.

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9. 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.

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