title: Vitreous IGFBP-3 effects on Müller cell proliferation and tractional force generation.
abstract: OBJECTIVE
  Previous studies from this laboratory revealed that vitreous insulin-like growth factor binding protein-3 (IGFBP-3) is a biologically active fragment of the intact protein. The goal of this study was to characterize its effects on Müller cell proliferation and tractional force generation, activities relevant to proliferative diabetic retinopathy (PDR).
  
  
  METHODS
  Müller cells were isolated from normal porcine retina. The vitreous-type IGFBP-3 fragment was isolated from normal human plasma and compared with intact recombinant protein for the ability to modulate Müller cell proliferation and tractional force generation in tissue culture models.
  
  
  RESULTS
  Müller cells were stimulated to proliferate by serum and platelet-derived growth factor (PDGF), but not insulin-like growth factor (IGF)-I or IGF-II. The cells were similarly unresponsive to IGFBP-3 or the IGFBP-3 fragment alone or in combination with IGF-I or IGF-II. In contrast, Müller cells demonstrated robust extracellular matrix contraction in response to IGF-I, IGF-II, and PDGF. Intact IGFBP-3 attenuated extracellular matrix contraction in response to IGF-I and IGF-II while the IGFBP-3 fragment modulated cell responses to IGF-II only. Neither binding protein altered cell responses to PDGF.
  
  
  CONCLUSIONS
  Intact IGFBP-3 modulates Müller cell tractional force generation stimulated by IGF-I and IGF-II while the effects of the vitreous-type fragment are limited to IGF-II. Porcine Müller cells proliferate in response to PDGF, but not IGF-I or IGF-II. Both forms of IGFBP-3 are also without mitogenic effects alone or in combination with IGFs. It appears that Müller cell tractional force generation in PDR is driven by vitreous IGF activity and proliferation is stimulated by growth factors outside of the IGF system.
authors: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama 35294, USA.
authors: Jeffery L
authors: JL
authors: King
authors: Clyde
authors: C
authors: Guidry
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D055351:Retinal Neurons / Q000166:cytology* / Q000378:metabolism; D013552:Swine; D014822:Vitreous Body / Q000502:physiology*
chemical_list: D024042:Collagen Type I; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D019394:Ki-67 Antigen; D010982:Platelet-Derived Growth Factor; D007334:Insulin-Like Growth Factor I