Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats.
Animals
Animals, Genetically Modified
Cell Transplantation
/ methods
Cyclic Nucleotide Phosphodiesterases, Type 6
/ deficiency
Disease Models, Animal
Gene Knockdown Techniques
Humans
Induced Pluripotent Stem Cells
/ cytology
Macular Degeneration
/ diagnosis
Rats
Retinal Pigment Epithelium
/ cytology
Journal
Experimental & molecular medicine
ISSN: 2092-6413
Titre abrégé: Exp Mol Med
Pays: United States
ID NLM: 9607880
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
26
11
2020
accepted:
31
01
2021
revised:
22
01
2021
pubmed:
9
4
2021
medline:
29
3
2022
entrez:
8
4
2021
Statut:
ppublish
Résumé
Retinal degenerative disorders, including age-related macular degeneration and retinitis pigmentosa (RP), are characterized by the irreversible loss of photoreceptor cells and retinal pigment epithelial (RPE) cells; however, the long-term effect of implanting both human induced pluripotent stem cell (hiPSC)-derived RPE and photoreceptor for retinal regeneration has not yet been investigated. In this study, we evaluated the long-term effects of hiPSC-derived RPE and photoreceptor cell transplantation in Pde6b knockout rats to study RP; cells were injected into the subretinal space of the right eyes of rats before the appearance of signs of retinal degeneration at 2-3 weeks of age. Ten months after transplantation, we evaluated the cells using fundus photography, optical coherence tomography, and histological evaluation, and no abnormal cell proliferation was observed. A relatively large number of transplanted cells persisted during the first 4 months; subsequently, the number of these cells decreased gradually. Notably, immunohistochemical analysis revealed that the hiPSC-derived retinal cells showed characteristics of both RPE cells and photoreceptors of human origin after transplantation. Functional analysis of vision by scotopic electroretinogram revealed significant preservation of vision after transplantation. Our study suggests that the transplantation of hiPSC-derived retinal cells, including RPE cells and photoreceptors, has a potential therapeutic effect against irreversible retinal degenerative diseases.
Identifiants
pubmed: 33828232
doi: 10.1038/s12276-021-00588-w
pii: 10.1038/s12276-021-00588-w
pmc: PMC8102536
doi:
Substances chimiques
Cyclic Nucleotide Phosphodiesterases, Type 6
EC 3.1.4.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
631-642Références
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