title: Vasoregression linked to neuronal damage in the rat with defect of polycystin-2.
abstract: BACKGROUND
  Neuronal damage is correlated with vascular dysfunction in the diseased retina, but the underlying mechanisms remain controversial because of the lack of suitable models in which vasoregression related to neuronal damage initiates in the mature retinal vasculature. The aim of this study was to assess the temporal link between neuronal damage and vascular patency in a transgenic rat (TGR) with overexpression of a mutant cilia gene polycystin-2.
  
  
  METHODS
  Vasoregression, neuroglial changes and expression of neurotrophic factors were assessed in TGR and control rats in a time course. Determination of neuronal changes was performed by quantitative morphometry of paraffin-embedded vertical sections. Vascular cell composition and patency were assessed by quantitative retinal morphometry of digest preparations. Glial activation was assessed by western blot and immunofluorescence. Expression of neurotrophic factors was detected by quantitative PCR.
  
  
  RESULTS
  At one month, number and thickness of the outer nuclear cell layers (ONL) in TGR rats were reduced by 31% (p<0.001) and 17% (p<0.05), respectively, compared to age-matched control rats. Furthermore, the reduction progressed from 1 to 7 months in TGR rats. Apoptosis was selectively detected in the photoreceptor in the ONL, starting after one month. Nevertheless, TGR and control rats showed normal responses in electroretinogram at one month. From the second month onwards, TGR retinas had significantly increased acellular capillaries (p<0.001), and a reduction of endothelial cells (p<0.01) and pericytes (p<0.01). Upregulation of GFAP was first detected in TGR retinas after 1 month in glial cells, in parallel with an increase of FGF2 (fourfold) and CNTF (60 %), followed by upregulation of NGF (40 %) at 3 months.
  
  
  CONCLUSIONS
  Our data suggest that TGR is an appropriate animal model for vasoregression related to neuronal damage. Similarities to experimental diabetic retinopathy render this model suitable to understand general mechanisms of maturity-onset vasoregression.
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Feng
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wang
authors.forename: Oliver
authors.initials: O
authors.lastname: Stock
authors.forename: Frederick
authors.initials: F
authors.lastname: Pfister
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D004596:Electroretinography / Q000379:methods; D005786:Gene Expression Regulation; D006720:Homozygote; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012160:Retina / Q000473:pathology; D055351:Retinal Neurons / Q000378:metabolism; D012171:Retinal Vessels / Q000473:pathology*; D050396:TRPP Cation Channels / Q000235:genetics* / Q000378:metabolism*
chemical_list: D050396:TRPP Cation Channels