2005 Fiscal Year Final Research Report Summary
Transplantation of enriched photoreceptor precursor cells into degenerated retina and conditioning of host retina.
| Project/Area Number |
16591748
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Kyoto University |
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Principal Investigator |
AKIMOTO Masayuki Kyoto University, Medicine, Assistant Professor, 医学研究科, 助手 (90303453)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Masayo Kyoto University, Medicine, Associate Professor, 医学研究科, 助教授 (80252443)
MANDAI Michiko Kyoto University, Medicine, Assistant Professor, 医学研究科, 助手 (80263086)
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| Project Period (FY) |
2004 – 2005
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| Keywords | photoreceptor / regenerative medicine / transgenic mice / retinal transplantation / in situ hybridization |
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| Research Abstract |
We previously generated transgenic mice (NrlGFP mice) in which the photoreceptor and its precursor cells are labeled by GFP. We tested the usefulness of this transgenic mice for retinal transplantation study. In first, we investigated the effect of enriched photoreceptor precursor cells into degenerated retina histologically and physiologically. We tested if the treatment with chondroitinase ABC (ChABC), an enzyme that degrades chondroitin sulfate proteoglycans, can promote synapse formation between graft and host neurons following retinal transplantation. We also investigated the gene profile of photoreceptor like cells transdifferentiated from iris pigment epithelial (IPE) cells assisted by gene transfer.
Up to four weeks after transplantation, almost all the grafted GFP+ photoreceptor cells were widely distributed at the outer margin of the host retina where the photoreceptor layer was located originally. In the Nrl/ChABC group,33.6% of the GFP+ photoreceptors elaborated neurites horizontally or vertically, and 4.6% elaborated neurites toward the retina. These neurites extended over the glial seal at the graft-host interface, and established synaptic contacts with neurons in the host retina as determined by confocal microscopy and three-dimensional analysis. Although 30.7% cells (P=0.68) elaborated neurites in the Nrl group, only 1.2% cells (P<0.05) projected neurites towards the host tissue and synaptic contacts were rare.
Microarray analyses provided lists of photoreceptor specific and IPE specific genes. We are currently testing those genes as markers for effectiveness of transdifferetiation.
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