Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury

Jennifer L. Kielczewski, Ping Hu, Lynn C. Shaw, Sergio Li Calzi, Robert N. Mames, Tom A. Gardiner, Evan McFarland, Tailoi Chan-Ling, Maria B. Grant

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

This study was conducted to determine the perivascular cell responses to increased endothelial cell expression of insulin-like growth factor binding protein-3 (IGFBP-3) in mouse retina. The contribution of bone marrow cells in the IGFBP-3-mediated response was examined using green fluorescent protein-positive (GFP+) adult chimeric mice subjected to laser-induced retinal vessel occlusion injury. Intravitreal injection of an endothelial-specific IGFBP-3- expressing plasmid resulted in increased differentiation of GFP+ hematopoietic stem cells (HSCs) into pericytes and astrocytes as determined by immunohistochemical analysis. Administration of IGFBP-3 plasmid to mouse pups that underwent the oxygen-induced retinopathy model resulted in increased pericyte ensheathment and reduced pericyte apoptosis in the developing retina. Increased IGFBP-3 expression reduced the number of activated microglial cells and decreased apoptosis of neuronal cells in the oxygen-induced retinopathy model. In summary, IGFBP-3 increased differentiation of GFP+ HSCs into pericytes and astrocytes while increasing vascular ensheathment of pericytes and decreasing apoptosis of pericytes and retinal neurons. All of these cytoprotective effects exhibited by IGFBP-3 overexpression can result in a more stable retinal vascular bed. Thus, endothelial expression of IGFBP-3 may represent a physiologic response to injury and may represent a therapeutic strategy for the treatment of ischemic vascular eye diseases, such as diabetic retinopathy and retinopathy of prematurity.

Original languageEnglish (US)
Pages (from-to)1517-1528
Number of pages12
JournalAmerican Journal of Pathology
Volume178
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

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Pericytes
Insulin-Like Growth Factor Binding Protein 3
Apoptosis
Wounds and Injuries
Retinal Vessels
Hematopoietic Stem Cells
Astrocytes
Retina
Plasmids
Oxygen
Retinal Neurons
Retinopathy of Prematurity
Intravitreal Injections
Eye Diseases
Neuroprotection
Diabetic Retinopathy
Green Fluorescent Proteins
Vascular Diseases
Bone Marrow Cells
Blood Vessels

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury. / Kielczewski, Jennifer L.; Hu, Ping; Shaw, Lynn C.; Li Calzi, Sergio; Mames, Robert N.; Gardiner, Tom A.; McFarland, Evan; Chan-Ling, Tailoi; Grant, Maria B.

In: American Journal of Pathology, Vol. 178, No. 4, 04.2011, p. 1517-1528.

Research output: Contribution to journalArticle

Kielczewski, Jennifer L. ; Hu, Ping ; Shaw, Lynn C. ; Li Calzi, Sergio ; Mames, Robert N. ; Gardiner, Tom A. ; McFarland, Evan ; Chan-Ling, Tailoi ; Grant, Maria B. / Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury. In: American Journal of Pathology. 2011 ; Vol. 178, No. 4. pp. 1517-1528.
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