title: Molecular responses of choroidal endothelial cells to elastin derived peptides through the elastin-binding protein (GLB1).
abstract: OBJECTIVE
  Neovascular AMD involves the activation of choroidal endothelial cells to increase their inflammatory and angiogenic behaviors. Elastin derived peptides (EDPs) can elicit some of these phenotypic changes in endothelial cells. This investigation was performed to follow up on those findings by determining a receptor for these peptides in the human eye as well as evaluating the effects of elevated EDPs on choroidal cells in vitro and in vivo.
  
  
  METHODS
  The expression of elastin receptor genes including GLB1 was analyzed using reverse transcription PCR. Migration of choroidal endothelial cells was quantified in the presence of inhibitors to different EDP binding proteins. C57BL6 mice were injected with EDPs and studied by electroretinography, transmission electron microscopy, and microarray analysis.
  
  
  RESULTS
  An alternatively spliced form of beta-galactosidase (GLB1) is present on human choroidal endothelial cells and acts as a receptor for EDPs. Elevated levels of circulating EDPs do not affect retinal function in the mouse, but do increase the expression and deposition of collagen IV in the RPE/choroid complex.
  
  
  CONCLUSIONS
  EDPs may play a role in neovascular AMD by binding to and inducing neovascular phenotypes in choroidal endothelial cells through their receptor, GLB1. These peptides also cause an increased mRNA expression and deposition of collagen IV in the RPE/choroid, which may alter diffusion properties between the retina and choriocapillaris.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Skeie
authors.forename: Jasmine
authors.initials: J
authors.lastname: Hernandez
authors.forename: Aleksander
authors.initials: A
authors.lastname: Hinek
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D016570:Bruch Membrane / Q000166:cytology*; D043402:Cathepsin A / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D054443:Cell Migration Assays; D002465:Cell Movement; D002829:Choroid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004058:Diffusion; D004549:Elastin / Q000494:pharmacology*; D004596:Electroretinography; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D004549:Elastin; C486385:NEU1 protein, human; D009439:Neuraminidase; C061901:GLB1 protein, human; D001616:beta-Galactosidase; C468629:CTSA protein, human; D043402:Cathepsin A