title: Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury.
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.
authors: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610-0267, USA.
authors: Jennifer L
authors: JL
authors: Kielczewski
authors: Ping
authors: P
authors: Hu
authors: Lynn C
authors: LC
authors: Shaw
authors: Sergio
authors: S
authors: Li Calzi
authors: Robert N
authors: RN
authors: Mames
authors: Tom A
authors: TA
authors: Gardiner
authors: Evan
authors: E
authors: McFarland
authors: Tailoi
authors: T
authors: Chan-Ling
authors: Maria B
authors: MB
authors: Grant
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology; D016923:Cell Death; D002454:Cell Differentiation; D005128:Eye Diseases / Q000473:pathology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D009474:Neurons / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology / Q000378:metabolism*; D012160:Retina / Q000293:injuries* / Q000378:metabolism
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D049452:Green Fluorescent Proteins