HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Dhomen, N. S. Articles by Sowden, J. C. Search for Related Content PubMed PubMed Citation Articles by Dhomen, N. S. Articles by Sowden, J. C.

Absence of Chx10 Causes Neural Progenitors to Persist in the Adult Retina

¹From the Developmental Biology Unit, Institute of Child Health, and the ²Institute of Ophthalmology, University College of London, London, United Kingdom; and the ³John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.

PURPOSE. Mutation of the Chx10 homeobox gene in mice and humans causes congenital blindness and microphthalmia (small eyes). This study used Chx10^–/– (ocular retardation) mice to investigate how lack of Chx10 affects progenitor/stem cell behavior in the retina and ciliary epithelium (CE).

METHODS. The distribution of mitotic retinal progenitor cells (RPCs) during embryonic development was analyzed using phosphohistone 3 (H3)-labeling. DNA flow cytometry was used to measure DNA content. The distribution and phenotype of dividing cells in the postnatal retina and CE was analyzed by incorporation of the thymidine analogue BrdU and immunohistochemistry.

RESULTS. The Chx10^–/– embryonic retina maintained a constantly sized population of mitotic RPCs during development, causing the mitotic index to increase markedly over time compared with the wild type. Also, the proportion of cells in the G₁ phase of the cell cycle was increased compared with the wild type. Of interest, division of RPC-like cells with neurogenic properties persisted in the adult Chx10^–/– retina. Colabeling for BrdU and the neural progenitor marker nestin or the neuronal markers ß3-tubulin, syntaxin, and VC1.1 showed that new amacrine-like neurons developed in the adult central retina. By contrast, cells with these characteristics were not observed in the mature wild-type retina. In the mature CE, BrdU-positive cells were observed in both wild-type and Chx10^–/– mice. However, neurogenesis from this cell population was not evident.

CONCLUSIONS. Without Chx10, proliferative expansion of the embryonic RPC pool is markedly reduced. In the adult retina, lack of Chx10 results in a population of dividing neural progenitor cells that persist and produce new neurons in the central retina.

This article has been cited by other articles:

				D. Damiani, J. J. Alexander, J. R. O'Rourke, M. McManus, A. P. Jadhav, C. L. Cepko, W. W. Hauswirth, B. D. Harfe, and E. Strettoi Dicer Inactivation Leads to Progressive Functional and Structural Degeneration of the Mouse Retina J. Neurosci., May 7, 2008; 28(19): 4878 - 4887. [Abstract] [Full Text] [PDF]

				K. M. Nishiguchi, H. Kaneko, M. Nakamura, S. Kachi, and H. Terasaki Identification of Photoreceptor Precursors in the Pars Plana during Ocular Development and after Retinal Injury Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 422 - 428. [Abstract] [Full Text] [PDF]