title: Lama1 mutations lead to vitreoretinal blood vessel formation, persistence of fetal vasculature, and epiretinal membrane formation in mice.
abstract: BACKGROUND
  Valuable insights into the complex process of retinal vascular development can be gained using models with abnormal retinal vasculature. Two such models are the recently described mouse lines with mutations in Lama1, an important component of the retinal internal limiting membrane (ILM). These mutants have a persistence of the fetal vasculature of vitreous (FVV) but lack a primary retinal vascular plexus. The present study provides a detailed analysis of astrocyte and vascular development in these Lama1 mutants.
  
  
  RESULTS
  Although astrocytes and blood vessels initially migrate into Lama1 mutant retinas, both traverse the peripapillary ILM into the vitreous by P3. Once in the vitreous, blood vessels anastomose with vessels of the vasa hyaloidea propria, part of the FVV, and eventually re-enter the retina where they dive to form the inner and outer retinal capillary networks. Astrocytes continue proliferating within the vitreous to form a dense mesh that resembles epiretinal membranes associated with persistent fetal vasculature and proliferative vitreoretinopathy.
  
  
  CONCLUSIONS
  Lama1 and a fully intact ILM are required for normal retinal vascular development. Mutations in Lama1 allow developing retinal vessels to enter the vitreous where they anastomose with vessels of the hyaloid system which persist and expand. Together, these vessels branch into the retina to form fairly normal inner retinal vascular capillary plexi. The Lama1 mutants described in this report are potential models for studying the human conditions persistent fetal vasculature and proliferative vitreoretinopathy.
authors: The Wilmer Eye Institute, Baltimore, MD 21287, USA.
authors: Malia M
authors: MM
authors: Edwards
authors: D Scott
authors: DS
authors: McLeod
authors: Rhonda
authors: R
authors: Grebe
authors: Céline
authors: C
authors: Heng
authors: Olivier
authors: O
authors: Lefebvre
authors: Gerard A
authors: GA
authors: Lutty
mesh_terms: D000818:Animals; D019773:Epiretinal Membrane / Q000196:embryology / Q000378:metabolism*; D007797:Laminin / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D012171:Retinal Vessels / Q000196:embryology / Q000254:growth & development*; D018630:Vitreoretinopathy, Proliferative / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D014822:Vitreous Body / Q000098:blood supply* / Q000196:embryology / Q000254:growth & development
chemical_list: D007797:Laminin; C084098:laminin A