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Open Access Adequate Time Window and Environmental Factors Supporting Retinal Graft Cell Survival in rd Mice

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Abstract:

Postnatal photoreceptor cells can be integrated into the wild-type adult retina in mice, and retinal transplantation is now one therapeutic option for retinal degenerative diseases when photoreceptor degeneration is the primary cause of the disease. The aim of this study was to specify the optimal time window during the course of retinal degeneration and to modulate the host and/or graft environment for a successful transplantation. We first studied the background features of the mice with phosphodiesterase 6b (PDE6b) gene mutation (rd; C3H/Hej) and found that the infiltration of microglia and glial fibrillary acidic protein (GFAP) expression once increased at the peak of rod death (∼2‐3 weeks of age) but then reduced for a following period until gliosis began to take place with enhanced GFAP expression (∼8 weeks of age). The postnatal retinal cells (p4‐p7) were successfully transplanted during this period with neurite extension into the host retina. In later transplantations (6 or 8 weeks of age), graft cells survived better in the presence of chondroitinase ABC (ChABC), which digests chondroitin sulfate proteoglycan (CSPG), an essential component of gliosis. In contrast, in earlier transplantations (4 weeks of age), graft cells survived better in the presence of valproic acid (VPA), a neural differentiating reagent, or glatiramer acetate, an immune modulator. These suggest that, immediately after the outer nuclear layer (ONL) degeneration, an inflammatory reaction may be easily induced but the host neurons may be more able to accept donor cells in the presence of neural differentiating factor. These results will help optimize transplantation conditions when we consider clinical application.

Keywords: Glatiramer acetate; Gliosis; Microglia; Photoreceptors; Transplantation; Valproic acid

Document Type: Research Article

DOI: https://doi.org/10.3727/215517912X639315

Affiliations: Laboratory for Retinal Regeneration, Riken Kobe CDB, Kobe, Hyogo, Japan

Publication date: 2012-01-01

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  • The importance of translating original, peer-reviewed research and review articles on the subject of cell therapy and its application to human diseases to society has led to the formation of the journal Cell Medicine. To ensure high-quality contributions from all areas of transplantation, the same rigorous peer review will be applied to articles published in Cell Medicine. Articles may deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, and stem cells, among others. Basic clinical studies and immunological research papers may also be featured if they have a translational interest. To provide complete coverage of this revolutionary field, Cell Medicine will report on relevant technological advances and their potential for translational medicine. Cell Medicine will be a purely online Open Access journal. There will therefore be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow your work to be disseminated to a wider audience and also entitle you to a free PDF, as well as prepublication of an unedited version of your manuscript.
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