title: Characterization of Retinal Vascular and Neural Damage in a Novel Model of Diabetic Retinopathy.
abstract: OBJECTIVE
  Diabetic retinopathy (DR) is a major cause of blindness globally. Investigating the underlying mechanisms of DR would be aided by a suitable mouse model that developed key features seen in the human disease, and did so without carrying genetic modifications. This study was undertaken to produce such a model.
  
  
  METHODS
  Our panel of Collaborative Cross strains was screened for DR-like features after induction of diabetes by intravenous injection with alloxan or streptozotocin. Both flat-mounted whole-retina and histologic sections were studied for the presence of retinal lesions. Progression of DR was also studied by histologic examination of the retinal vascular and neural structure at various time points after diabetes onset. In addition, microarray investigations were conducted on retinas from control and diabetic mice.
  
  
  RESULTS
  Features of DR such as degenerated pericytes, acellular capillaries, minor vascular proliferation, gliosis of Müller cells, and loss of ganglion cells were noted as early as day 7 in some mice. These lesions became more evident with time. After 21 days of diabetes, severe vascular proliferation, microaneurysms, preretinal damage, increased Müller cell gliosis, and damage to the outer retina were all obvious. Microarray studies found significant differential expression of multiple genes known to be involved in DR.
  
  
  CONCLUSIONS
  The FOT_FB strain provides a useful model to investigate the pathogenesis of DR and to develop treatments for this vision-threatening disease.
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia 2Centre of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Lakshini Y
authors.initials: LY
authors.lastname: Weerasekera
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia 2Centre of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia 3School.
authors.forename: Lois A
authors.initials: LA
authors.lastname: Balmer
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia 2Centre of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ram
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia 2Centre of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
mesh_terms: D000818:Animals; D003930:Diabetic Retinopathy / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D012164:Retinal Diseases / Q000209:etiology*; D012171:Retinal Vessels