Vasoregression Linked to Neuronal Damage in the Rat with Defect of Polycystin-2Reportar como inadecuado

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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.


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.


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.


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.

Autor: Yuxi Feng, Yumei Wang , Oliver Stock , Frederick Pfister, Naoyuki Tanimoto, Mathias W. Seeliger, Jan-Luuk Hillebrands, Sigrid Hof



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