Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors.
OBJECTIVE
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.
Sengupta
Nilanjana
N
Program in Stem Cell Biology, University of Florida, Gainesville, Florida 32510-0267, USA.
Caballero
Sergio
S
Mames
Robert N
RN
Timmers
Adrian M
AM
Saban
Daniel
D
Grant
Maria B
MB
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D015703:Antigens, CD; D015820:Cadherins / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology; D002678:Chimera; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000502:physiology*; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D017075:Laser Coagulation; D008164:Luminescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D000099152:Cadherin 5
D000906:Antibodies; D015703:Antigens, CD; D015820:Cadherins; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000099152:Cadherin 5; C515256:Cxcl12 protein, mouse