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 Li, Y. Articles by Enzmann, V. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Enzmann, V.

Retinal Pigment Epithelium Damage Enhances Expression of Chemoattractants and Migration of Bone Marrow–Derived Stem Cells

¹From the Department of Ophthalmology and Visual Sciences, the ²Stem Cell Program, Department of Medicine, and the ³Institute for Cellular Therapeutics, University of Louisville, Louisville, Kentucky.

PURPOSE. To characterize chemoattractants expressed by the retinal pigment epithelium (RPE) after sodium iodate (NaIO₃)–induced damage and to investigate whether ocular-committed stem cells preexist in the bone marrow (BM) and migrate in response to the chemoattractive signals expressed by the damaged RPE.

METHODS. C57/BL6 mice were treated with a single intravenous injection of NaIO₃ (50 mg/kg) to create RPE damage. At different time points real-time RT-PCR, ELISA, and immunohistochemistry were used to identify chemoattractants secreted in the subretinal space. Conditioned medium from NaIO₃-treated mouse RPE was used in an in vitro assay to assess chemotaxis of stem cell antigen-1 positive (Sca-1⁺) BM mononuclear cells (MNCs). The expression of early ocular markers (MITF, Pax-6, Six-3, Otx) in migrated cells and in MNCs isolated from granulocyte colony–stimulating factor (G-CSF) and Flt3 ligand (FL)–mobilized and nonmobilized peripheral blood (PB) was analyzed by real-time RT-PCR.

RESULTS. mRNA for stromal cell–derived factor-1 (SDF-1), C3, hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF) was significantly increased, and higher SDF-1 and C3 protein secretion from the RPE was found after NaIO₃treatment. A higher number of BMMNCs expressing early ocular markers migrated to conditioned medium from damaged retina. There was also increased expression of early ocular markers in PBMNCs after mobilization.

CONCLUSIONS. Damaged RPE secretes cytokines that have been shown to serve as chemoattractants for BM-derived stem cells (BMSCs). Retina-committed stem cells appear to reside in the BM and can be mobilized into the PB by G-CSF and FL. These stem cells may have the potential to serve as an endogenous source for tissue regeneration after RPE damage.

This article has been cited by other articles:

				P. Charalambous, L. A. Hurst, and S. Thanos Engrafted Chicken Neural Tube-Derived Stem Cells Support the Innate Propensity for Axonal Regeneration within the Rat Optic Nerve Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3513 - 3524. [Abstract] [Full Text] [PDF]

				C Boettcher, E Ulbricht, D Helmlinger, A F Mack, A Reichenbach, P Wiedemann, H-J Wagner, M W Seeliger, A Bringmann, and J Priller Long-term engraftment of systemically transplanted, gene-modified bone marrow-derived cells in the adult mouse retina Br. J. Ophthalmol., February 1, 2008; 92(2): 272 - 275. [Abstract] [Full Text] [PDF]

				Y. Yodoi, M. Sasahara, T. Kameda, N. Yoshimura, and A. Otani Circulating Hematopoietic Stem Cells in Patients with Neovascular Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5464 - 5472. [Abstract] [Full Text] [PDF]

				Y. Li, P. Atmaca-Sonmez, C. L. Schanie, S. T. Ildstad, H. J. Kaplan, and V. Enzmann Endogenous Bone Marrow Derived Cells Express Retinal Pigment Epithelium Cell Markers and Migrate to Focal Areas of RPE Damage Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4321 - 4327. [Abstract] [Full Text] [PDF]