Hematopoietic stem cells provide repair functions after laser-induced Bruch's membrane rupture model of choroidal neovascularization

Tailoi Chan-Ling, Louise Baxter, Aqeela Afzal, Nilanjana Sengupta, Sergio Caballero, Emilia Rosinova, Maria B. Grant

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Vascular repair by adult hematopoietic stem cells (HSCs) is well-appreciated because these cells are known for their plasticity. We have shown that adult HSCs differentiate into endothelial cells and participate in both retinal and choroidal neovascularization. We asked whether HSCs participated in the wounding response by forming astrocytes, retinal pigment epithelia (RPE), macrophages, and pericytes. Lethally irradiated C57BL6/J mice were reconstituted with HSCs from mice homozygous for green fluorescent protein (GFP) and then subjected to laser-induced rupture of Bruch's membrane. After immunohistochemical examination of ocular tissue, GFP+ astrocytes were observed concentrated along the edge of the laser wound, where they and mural cells closely ensheathed the neovasculature. GFP+ vascular endothelial cells and macrophages/microglia were also evident. Large irregularly shaped GFP+ RPE cells constituted ∼93% of MPE cells adjacent to the edge of the denuded RPE area. In regions farther away from the wound, GFP+ RPE cells were integrated among the GFP- host RPE. Thus, postnatal HSCs can differentiate into cells expressing markers specific to astrocytes, macrophages/microglia, mural cells, or RPE. These studies suggest that HSCs could serve as a therapeutic source for long-term regeneration of injured retina and choroid in diseases such as age-related macular degeneration and retinitis pigmentosa.

Original languageEnglish (US)
Pages (from-to)1031-1044
Number of pages14
JournalAmerican Journal of Pathology
Volume168
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

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Bruch Membrane
Choroidal Neovascularization
Hematopoietic Stem Cells
Retinal Pigment Epithelium
Green Fluorescent Proteins
Rupture
Lasers
Astrocytes
Adult Stem Cells
Macrophages
Microglia
Choroid Diseases
Endothelial Cells
Retinal Neovascularization
Pericytes
Retinitis Pigmentosa
Wounds and Injuries
Macular Degeneration
Blood Vessels
Retina

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Hematopoietic stem cells provide repair functions after laser-induced Bruch's membrane rupture model of choroidal neovascularization. / Chan-Ling, Tailoi; Baxter, Louise; Afzal, Aqeela; Sengupta, Nilanjana; Caballero, Sergio; Rosinova, Emilia; Grant, Maria B.

In: American Journal of Pathology, Vol. 168, No. 3, 03.2006, p. 1031-1044.

Research output: Contribution to journalArticle

Chan-Ling, Tailoi ; Baxter, Louise ; Afzal, Aqeela ; Sengupta, Nilanjana ; Caballero, Sergio ; Rosinova, Emilia ; Grant, Maria B. / Hematopoietic stem cells provide repair functions after laser-induced Bruch's membrane rupture model of choroidal neovascularization. In: American Journal of Pathology. 2006 ; Vol. 168, No. 3. pp. 1031-1044.
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