IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2007;48:446-454.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0190
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (15)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Canola, K.
Right arrow Articles by Arsenijevic, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Canola, K.
Right arrow Articles by Arsenijevic, Y.

Retinal Stem Cells Transplanted into Models of Late Stages of Retinitis Pigmentosa Preferentially Adopt a Glial or a Retinal Ganglion Cell Fate

Kriss Canola,1 Brigitte Angénieux,1 Meriem Tekaya,1 Alexander Quiambao,2 Muna I. Naash,2 Francis L. Munier,3 Daniel F. Schorderet,4 and Yvan Arsenijevic1

1From the Unit of Gene Therapy and Stem Cell Biology, and 3Unit of Clinical Oculogenetics, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland; the 4Institute of Research in Ophthalmology, Sion, Switzerland; and the 2Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

PURPOSE. To characterize the potential of newborn retinal stem cells (RSCs) isolated from the radial glia population to integrate the retina, this study was conducted to investigate the fate of in vitro expanded RSCs transplanted into retinas devoid of photoreceptors (adult rd1 and old VPP mice and rhodopsin-mutated transgenic mice) or partially degenerated retina (adult VPP mice) retinas.

METHODS. Populations of RSCs and progenitor cells were isolated either from DBA2J newborn mice and labeled with the red lipophilic fluorescent dye (PKH26) or from GFP (green fluorescent protein) transgenic mice. After expansion in EGF+FGF2 (epidermal growth factor+fibroblast growth factor), cells were transplanted intravitreally or subretinally into the eyes of adult wild-type, transgenic mice undergoing slow (VPP strain) or rapid (rd1 strain) retinal degeneration.

RESULTS. Only limited migration and differentiation of the cells were observed in normal mice injected subretinally or in VPP and rd1 mice injected intravitreally. After subretinal injection in old VPP mice, transplanted cells massively migrated into the ganglion cell layer and, at 1 and 4 weeks after injection, harbored neuronal and glial markers expressed locally, such as ß-tubulin-III, NeuN, Brn3b, or glial fibrillary acidic protein (GFAP), with a marked preference for the glial phenotype. In adult VPP retinas, the grafted cells behaved similarly. Few grafted cells stayed in the degenerating outer nuclear layer (ONL). These cells were, in rare cases, positive for rhodopsin or recoverin, markers specific for photoreceptors and some bipolar cells.

CONCLUSIONS. These results show that the grafted cells preferentially integrate into the GCL and IPL and express ganglion cell or glial markers, thus exhibiting migratory and differentiation preferences when injected subretinally. It also appears that the retina, whether partially degenerated or already degenerated, does not provide signals to induce massive differentiation of RSCs into photoreceptors. This observation suggests that a predifferentiation of RSCs into photoreceptors before transplantation may be necessary to obtain graft integration in the ONL.




This article has been cited by other articles:


Home page
 IOVSHome page
J. Sancho-Pelluz, K. A. Wunderlich, U. Rauch, F. J. Romero, T. van Veen, G. A. Limb, P. R. Crocker, and M.-T. Perez
Sialoadhesin Expression in Intact Degenerating Retinas and Following Transplantation
Invest. Ophthalmol. Vis. Sci., December 1, 2008; 49(12): 5602 - 5610.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. Bosco, D. M. Inman, M. R. Steele, G. Wu, I. Soto, N. Marsh-Armstrong, W. C. Hubbard, D. J. Calkins, P. J. Horner, and M. L. Vetter
Reduced Retina Microglial Activation and Improved Optic Nerve Integrity with Minocycline Treatment in the DBA/2J Mouse Model of Glaucoma
Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1437 - 1446.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
S. Singhal, J. M. Lawrence, B. Bhatia, J. S. Ellis, A. S. Kwan, A. MacNeil, P. J. Luthert, J. W. Fawcett, M.-T. Perez, P. T. Khaw, et al.
Chondroitin Sulfate Proteoglycans and Microglia Prevent Migration and Integration of Grafted Muller Stem Cells into Degenerating Retina
Stem Cells, April 1, 2008; 26(4): 1074 - 1082.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
B. P. Buckingham, D. M. Inman, W. Lambert, E. Oglesby, D. J. Calkins, M. R. Steele, M. L. Vetter, N. Marsh-Armstrong, and P. J. Horner
Progressive Ganglion Cell Degeneration Precedes Neuronal Loss in a Mouse Model of Glaucoma
J. Neurosci., March 12, 2008; 28(11): 2735 - 2744.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
T. F. Ng, N. Kitaichi, and A. W. Taylor
In Vitro Generated Autoimmune Regulatory T Cells Enhance Intravitreous Allogeneic Retinal Graft Survival
Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5112 - 5117.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the Association for Research in Vision and Ophthalmology