Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization
Résumé
Aims
Branch retinal vein occlusion (BRVO) leads to extensive vascular remodeling and is important
cause of visual impairment. Although the vascular morphological changes following
experimental vein occlusion have been described in a variety of models using angiography,
the underlying cellular events are ill defined.
Methods and Results
We here show that laser-induced experimental BRVO in mice leads to a wave of TUNELpositive
endothelial cell (EC) apoptosis in the upstream vascular network associated with
a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation
within the dilated vein and capillaries, detected by EdU incorporation, and the
edema resolves. However, the pericytes of the upstream capillaries are severely reduced,
which was associated with continuing EC apoptosis and proliferation. The vascular remodeling
was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression.
Exposure of the experimental animals to hypoxia, when pericyte (PC) dropout had
occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular
instability induced by the experimental BRVO.
Conclusion
Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability.
Subsequently the upstream vascular network remains destabilized, characterized by pericyte
dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia.
These early changes might pave the way for capillary loss and subsequent chronic ischemia
and edema that characterize the late stage disease.
Domaines
Neurosciences [q-bio.NC]
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