Phagocytosis of Photoreceptor Outer Segments by Transplanted Human Neural Stem Cells as a Neuroprotective Mechanism in Retinal Degeneration

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Title: Phagocytosis of Photoreceptor Outer Segments by Transplanted Human Neural Stem Cells as a Neuroprotective Mechanism in Retinal Degeneration
Authors: Cuenca, Nicolás | Fernández Sánchez, Laura | McGill, Trevor J. | Lu, Bin | Wang, Shaomei | Lund, Raymond D. | Huhn, Stephen | Capela, Alexandra
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: Transplant | Therapy | Electron microscopy | Phagocytosis | Synaptic contacts | Retinal degeneration
Knowledge Area: Biología Celular
Issue Date: 15-Oct-2013
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Citation: Investigative Ophthalmology & Visual Science. 2013, 54(10): 6745-6756. doi:10.1167/iovs.13-12860
Abstract: Purpose. Transplantation of human central nervous system stem cells (HuCNS-SC) into the subretinal space of Royal College of Surgeons (RCS) rats preserves photoreceptors and visual function. To explore possible mechanism(s) of action underlying this neuroprotective effect, we performed a detailed morphologic and ultrastructure analysis of HuCNS-SC transplanted retinas. Methods. The HuCNS-SC were transplanted into the subretinal space of RCS rats. Histologic examination of the transplanted retinas was performed by light and electron microscopy. Areas of the retina adjacent to HuCNS-SC graft (treated regions) were analyzed and compared to control sections obtained from the same retina, but distant from the transplant site (untreated regions). Results. The HuCNS-SC were detected as a layer of STEM 121 immunopositive cells in the subretinal space. In treated regions, preserved photoreceptor nuclei, as well as inner and outer segments were identified readily. In contrast, classic signs of degeneration were observed in the untreated regions. Interestingly, detailed ultrastructure analysis revealed a striking preservation of the photoreceptor–bipolar–horizontal cell synaptic contacts in the outer plexiform layer (OPL) of treated areas, in stark contrast with untreated areas. Finally, the presence of phagosomes and vesicles exhibiting the lamellar structure of outer segments also was detected within the cytosol of HuCNS-SC, indicating that these cells have phagocytic capacity in vivo. Conclusions. This study reveals the novel finding that preservation of specialized synaptic contacts between photoreceptors and second order neurons, as well as phagocytosis of photoreceptor outer segments, are potential mechanism(s) of HuCNS-SC transplantation, mediating functional rescue in retinal degeneration.
Sponsor: Supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2012-36845), Instituto de Salud Carlos III (RETICS RD12/0034/0010), Organización Nacional de Ciegos Españoles (ONCE), and StemCells, Inc. (NC).
URI: http://hdl.handle.net/10045/40109
ISSN: 0146-0404 (Print) | 1552-5783 (Online)
DOI: 10.1167/iovs.13-12860
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2013 The Association for Research in Vision and Ophthalmology, Inc.
Peer Review: si
Publisher version: http://dx.doi.org/10.1167/iovs.13-12860
Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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