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

Nilanjana Sengupta, Sergio Caballero, Robert N. Mames, Adrian M. Timmers, Daniel Saban, Maria B. Grant

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)343-348
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

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Choroidal Neovascularization
Stem Cells
Hematopoietic Stem Cells
Green Fluorescent Proteins
Choroid
Light Coagulation
Macular Degeneration
Lasers
Bone Marrow
Bruch Membrane
Sclera
Adult Stem Cells
Antibodies
Inbred C57BL Mouse
Fluorescence Microscopy
Developed Countries
Cell Adhesion
Retina
Rupture
Endothelial Cells

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors. / Sengupta, Nilanjana; Caballero, Sergio; Mames, Robert N.; Timmers, Adrian M.; Saban, Daniel; Grant, Maria B.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 1, 01.2005, p. 343-348.

Research output: Contribution to journalArticle

Sengupta, Nilanjana ; Caballero, Sergio ; Mames, Robert N. ; Timmers, Adrian M. ; Saban, Daniel ; Grant, Maria B. / Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 1. pp. 343-348.
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abstract = "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.",
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N2 - 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.

AB - 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.

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