Retinal pigment epithelium damage enhances expression of chemoattractants and migration of bone marrow-derived stem cells

Li, Yang; Reca, Ryan G; Atmaca-Sonmez, Pelin; Ratajczak, Mariusz Z; Ildstad, Suzanne T; Kaplan, Henry J; Enzmann, Volker (2006). Retinal pigment epithelium damage enhances expression of chemoattractants and migration of bone marrow-derived stem cells. Investigative ophthalmology & visual science, 47(4), pp. 1646-52. Hagerstown, Md.: Association for Research in Vision and Ophthalmology 10.1167/iovs.05-1092

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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 NaIO3 treatment. 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Enzmann, Volker

ISSN:

0146-0404

ISBN:

16565405

Publisher:

Association for Research in Vision and Ophthalmology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:49

Last Modified:

06 Dec 2013 13:43

Publisher DOI:

10.1167/iovs.05-1092

PubMed ID:

16565405

Web of Science ID:

000236560800052

URI:

https://boris.unibe.ch/id/eprint/20442 (FactScience: 3740)

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