Dynamics of clinical and immunological parameters in retinal pigment epithelium transplantation in the context of combined immunosuppressive therapy in the rabbit model of retinal degeneration
- 作者: Neroeva N.V.1, Balatskaya N.V.1, Neroev V.V.1, Brilliantova A.G.1, Katargina L.A.1, Lagarkova M.A.2
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隶属关系:
- Helmholtz National Medical Research Eye Diseases Center
- Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency
- 期: 卷 27, 编号 4 (2024)
- 页面: 787-794
- 栏目: SHORT COMMUNICATIONS
- URL: https://ogarev-online.ru/1028-7221/article/view/267852
- DOI: https://doi.org/10.46235/1028-7221-16700-DOC
- ID: 267852
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Progressive damage of the retinal pigment epithelium (RPE) underlies the pathogenesis of degenerative retinal diseases such as: age-related macular degeneration (AMD), Stargardt’s disease, retinitis pigmentosa, Best’s disease and others. This group of diseases led by AMD leads to irreversible loss of visual functions, blindness and disability. The possibilities of therapy of late stages of AMD are extremely limited. The most promising approach to replace the damaged retinal pigment epithelium appears to be transplantation of RPE cells derived from induced pluripotent stem cells (iPSC-RPE) into the subretinal space (SRS). Despite immune privilege in the SRS, transplantation of xenogeneic cellular material causes severe inflammation in the posterior segment of the eye and leads to graft rejection in an in vivo experiment in the absence of immunosuppression. The solution to the problem of tissue incompatibility in this case can be the use of combined immunosuppressive therapy (CIT), aimed, on the one hand, at suppression of local inflammation (in the eye) and, on the other hand, at suppression of the systemic transplantation immune response. The aim of the study: clinical and immunological analysis of the results of transplantation of IPSC-RPE suspension on the background of CIT, including single intravitreal intraoperative administration of kenalog and further systemic application of mycophenolate mofetil (MMF), in the model of RPE atrophy in rabbits. Standard and specialized ophthalmological examination was performed at early and distant terms after the intervention in order to clinically assess the posttransplantation process. To analyze the immune status, vitreous humor (VH) and blood serum (BS) of rabbits of the experimental groups were collected. The concentrations of TGF-β1, TGF-β2, and IL-2 were determined in the biomaterial using solid-phase enzyme immunoassay. According to the results of the study, subretinal transplantation of IPSC-RPE, performed against the background of combination of single intravitreal intraoperative administration of kenalog and systemic application of MMF, is a safe method, which provides preservation of the retina and other adjacent structures of the eye and allows to prevent rejection of xenogenic material during its transplantation both in a healthy eye and with pre-formed RPE atrophy, which opens perspectives for full testing of biological effects realized by IPSC-RPE.
作者简介
N. Neroeva
Helmholtz National Medical Research Eye Diseases Center
Email: angelinabrilliantova@gmail.com
PhD (Medicine), Ophthalmologist, Department of Retinal and Optic Nerve Pathology
俄罗斯联邦, 14/19 Sadovaya-Chernogryazskaya St, Moscow, 105062N. Balatskaya
Helmholtz National Medical Research Eye Diseases Center
Email: angelinabrilliantova@gmail.com
PhD (Biology), Leading Research Associate, Head, Department of the Immunology and Virology
俄罗斯联邦, 14/19 Sadovaya-Chernogryazskaya St, Moscow, 105062V. Neroev
Helmholtz National Medical Research Eye Diseases Center
Email: angelinabrilliantova@gmail.com
PhD, MD (Medicine), Professor, Full Member, Russian Academy of Science, Director
俄罗斯联邦, 14/19 Sadovaya-Chernogryazskaya St, Moscow, 105062A. Brilliantova
Helmholtz National Medical Research Eye Diseases Center
编辑信件的主要联系方式.
Email: angelinabrilliantova@gmail.com
Postgraduate Student, Department of Retinal and Optic Nerve Pathology
俄罗斯联邦, 14/19 Sadovaya-Chernogryazskaya St, Moscow, 105062L. Katargina
Helmholtz National Medical Research Eye Diseases Center
Email: angelinabrilliantova@gmail.com
PhD, MD (Medicine), Professor, Head, Eye Pathology in Children Department, Deputy Director
俄罗斯联邦, 14/19 Sadovaya-Chernogryazskaya St, Moscow, 105062M. Lagarkova
Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency
Email: angelinabrilliantova@gmail.com
PhD, MD (Biology), Correxponding Member, Russian Academy of Science, Director
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