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Mycoplasma Ocular Infection in Subretinal Graft Transplantation of iPS Cells-Derived Retinal Pigment Epithelial Cells.
Invest Ophthalmol Vis Sci. 2019 04 01; 60(5):1298-1308.IO

Abstract

Purpose

To report occurrence of acute severe inflammation after surgical implantation of mycoplasma-infected induced pluripotent stem cell-derived RPE (iPS-RPE) cells into the eyes of healthy primates, and determine the immunopathological mechanisms of the inflammation.

Methods

Ophthalmic allogeneic transplantation of iPS-RPE cells was performed in the subretina of major histocompatibility complex (MHC)-matched (two eyes) and MHC-mismatched (one eye) healthy cynomolgus monkeys. The clinical course after transplantation was observed using color fundus photography, fluorescence angiography, and optical coherence tomography. After the animals were killed at 1 month after surgery, eyeballs were removed and pathologically examined. Microorganisms were analyzed by PCR methods and BLAST analysis using preserved graft iPS-RPE cells and the recipients' vitreous humor. Mixed lymphocyte-RPE assay was performed on the mycoplasma-infected and noninfected iPS-RPE cells in vitro.

Results

In tested eyes, abnormal findings were observed in the grafted retina 2 weeks after surgery. Here, we observed retinal vasculitis and hemorrhage, retinal detachment, and infiltration of inflammatory cells into the retina of the eyes. One month after surgery, animals were killed due to the severe immune responses observed. Using PCR methods, sequence analysis detected mycoplasma-DNA (Mycoplasma arginini species) in both the grafted RPE cells and the collected vitreous fluids of the monkeys. Mixed lymphocyte-RPE assay revealed that the infected iPS-RPE cells enhanced the proliferation of inflammatory cells in vitro.

Conclusions

Transplantation of graft iPS-RPE cells contaminated with mycoplasma into the subretina caused severe ocular inflammation. Mycoplasma possesses the ability to cause immune responses in the host.

Authors+Show Affiliations

Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, RIKEN, Kobe, Japan. Kyoto University Graduate School of Medicine, Kyoto, Japan.Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, RIKEN, Kobe, Japan.Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, RIKEN, Kobe, Japan.Department of Ophthalmology, Kawasaki Medical School, Okayama, Japan.Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, RIKEN, Kobe, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30933257

Citation

Makabe, Kenichi, et al. "Mycoplasma Ocular Infection in Subretinal Graft Transplantation of iPS Cells-Derived Retinal Pigment Epithelial Cells." Investigative Ophthalmology & Visual Science, vol. 60, no. 5, 2019, pp. 1298-1308.
Makabe K, Sugita S, Hono A, et al. Mycoplasma Ocular Infection in Subretinal Graft Transplantation of iPS Cells-Derived Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 2019;60(5):1298-1308.
Makabe, K., Sugita, S., Hono, A., Kamao, H., & Takahashi, M. (2019). Mycoplasma Ocular Infection in Subretinal Graft Transplantation of iPS Cells-Derived Retinal Pigment Epithelial Cells. Investigative Ophthalmology & Visual Science, 60(5), 1298-1308. https://doi.org/10.1167/iovs.18-26222
Makabe K, et al. Mycoplasma Ocular Infection in Subretinal Graft Transplantation of iPS Cells-Derived Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 2019 04 1;60(5):1298-1308. PubMed PMID: 30933257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mycoplasma Ocular Infection in Subretinal Graft Transplantation of iPS Cells-Derived Retinal Pigment Epithelial Cells. AU - Makabe,Kenichi, AU - Sugita,Sunao, AU - Hono,Ayumi, AU - Kamao,Hiroyuki, AU - Takahashi,Masayo, PY - 2019/4/2/entrez PY - 2019/4/2/pubmed PY - 2019/9/26/medline SP - 1298 EP - 1308 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 60 IS - 5 N2 - Purpose: To report occurrence of acute severe inflammation after surgical implantation of mycoplasma-infected induced pluripotent stem cell-derived RPE (iPS-RPE) cells into the eyes of healthy primates, and determine the immunopathological mechanisms of the inflammation. Methods: Ophthalmic allogeneic transplantation of iPS-RPE cells was performed in the subretina of major histocompatibility complex (MHC)-matched (two eyes) and MHC-mismatched (one eye) healthy cynomolgus monkeys. The clinical course after transplantation was observed using color fundus photography, fluorescence angiography, and optical coherence tomography. After the animals were killed at 1 month after surgery, eyeballs were removed and pathologically examined. Microorganisms were analyzed by PCR methods and BLAST analysis using preserved graft iPS-RPE cells and the recipients' vitreous humor. Mixed lymphocyte-RPE assay was performed on the mycoplasma-infected and noninfected iPS-RPE cells in vitro. Results: In tested eyes, abnormal findings were observed in the grafted retina 2 weeks after surgery. Here, we observed retinal vasculitis and hemorrhage, retinal detachment, and infiltration of inflammatory cells into the retina of the eyes. One month after surgery, animals were killed due to the severe immune responses observed. Using PCR methods, sequence analysis detected mycoplasma-DNA (Mycoplasma arginini species) in both the grafted RPE cells and the collected vitreous fluids of the monkeys. Mixed lymphocyte-RPE assay revealed that the infected iPS-RPE cells enhanced the proliferation of inflammatory cells in vitro. Conclusions: Transplantation of graft iPS-RPE cells contaminated with mycoplasma into the subretina caused severe ocular inflammation. Mycoplasma possesses the ability to cause immune responses in the host. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/30933257/Mycoplasma_Ocular_Infection_in_Subretinal_Graft_Transplantation_of_iPS_Cells_Derived_Retinal_Pigment_Epithelial_Cells_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.18-26222 DB - PRIME DP - Unbound Medicine ER -