Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors.

Published

Journal Article

PURPOSE: The primary cause of vision loss in people more than 50 years of age in developed nations is age-related macular degeneration (ARMD). The wet form of ARMD is characterized by choroidal neovascularization (CNV). A prior study has shown that adult hematopoietic stem cells (HSCs) contribute to approximately 50% of newly formed vasculature in CNV. Stromal-derived factor (SDF)-1 is involved with homing of HSCs from bone marrow to target tissue. Vascular endothelial cadherin (VE-cadherin, or CD144) is involved in endothelial cell adhesion. Preventing homing and/or adhesion of progenitor cells to damaged choroid could reduce CNV. METHODS: Adult C57BL/6J mice were lethally irradiated, and then received a transplant of purified c-kit+Sca-1+ HSCs from the bone marrow of green fluorescent protein (gfp) homozygous donor mice. Bruch's membrane rupture by laser photocoagulation was used to induce CNV. Animals were injected subretinally with anti-SDF-1, anti-CD144, or control, before or after laser photocoagulation. The eyes were enucleated, and the neural retinas were separated from the RPE/choroid/sclera complex. All tissues were flatmounted and qualitatively and quantitatively assessed by fluorescence microscopy. RESULTS: CNV lesions from eyes treated with anti-CD144 showed significantly less incorporation of gfp+ cells compared with those treated with anti-SDF-1. Antibody treatment generally reduced the degree of gfp+ stem cell recruitment and incorporation into the CNV lesions, compared with the control. Treatment with either antibody also significantly reduced the size of the CNV lesions. CONCLUSIONS: These results indicate that homing and adhesion of progenitor cells to CNV may be targeted differentially or in combination to prevent CNV.

Full Text

Duke Authors

Cited Authors

  • Sengupta, N; Caballero, S; Mames, RN; Timmers, AM; Saban, D; Grant, MB

Published Date

  • January 2005

Published In

Volume / Issue

  • 46 / 1

Start / End Page

  • 343 - 348

PubMed ID

  • 15623794

Pubmed Central ID

  • 15623794

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

International Standard Serial Number (ISSN)

  • 0146-0404

Digital Object Identifier (DOI)

  • 10.1167/iovs.04-0153

Language

  • eng