title: Blood Vessel Basement Membrane Alterations in Human Retinal Microaneurysms During Aging.
abstract: Microaneurysms, considered a hallmark of retinal vascular disease, are present in aged retinas. Here, the basement membrane of human retinal microaneurysms has been analyzed during aging.
  
  
  
  Retinas were obtained from 17 nondiabetic donors. Whole mount retinas and paraffin sections were marked immunohistochemically with antibodies against the main components of the blood basement membrane. Trypsin digestion and transmission electron microscopy also were performed.
  
  
  
  Small microaneurysms presented increased expression of collagen IV, laminin, fibronectin, nidogen, and perlecan, along with basement membrane thickening. Unexpectedly, crosslinked fibrils of collagen III, a type of collagen absent in retinal capillaries, were found specifically in small microaneurysms. This was parallel to enhanced lysyl oxidase-like (LOXL) 2 and 4 expression. Large microaneurysms showed diminution of protein content, as well as disorganization, in their basement membrane. This was concomitant with an increased expression of matrix-metalloproteinase (MMP)-9 and plasminogen activator inhibitor (PAI)-1. Pericyte coverage declined between small and large microaneurysms.
  
  
  
  Thickening of the basement membrane in small microaneurysms by accumulation of matrix proteins probably produced by recruited pericytes, together with the appearance of crosslinked collagen III fibrils probably due to the action of LOXL2 and LOXL4, could be considered as compensatory mechanisms to strengthen the vascular wall in the early phase of microaneurysm formation. Later, increased activity of MMP-9 and PAI-I, which produce disruption of the blood basement membrane and expansion of microthrombi respectively, and loss of pericytes, which produces weakening of the vascular wall, could explain the wall dilation observed in the late phase of microaneurysm formation.
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: López-Luppo
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain 2Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Nacher
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain 3Interdisciplinary Centre of Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: David
authors.initials: D
authors.lastname: Ramos
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain 2Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Catita
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain 2Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain 2Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Carretero
authors.affiliation: Department of Morphological Sciences, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rodriguez-Baeza
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain 3Interdisciplinary Centre of Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal 5Department of Morphology and Function, Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Mendes-Jorge
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain 2Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain 3Interdisciplinary Centre of Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal 6CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruberte
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D000071071:Microaneurysm / Q000175:diagnosis* / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D012164:Retinal Diseases / Q000175:diagnosis* / Q000378:metabolism; D012171:Retinal Vessels; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D020780:Matrix Metalloproteinase 9