Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy
Journal Title
Journal of Clinical Investigation
Publication Type
Journal epub ahead of print
Abstract
Aberrant, neovascular retinal blood vessel growth is a vision-threatening complication in ischemic retinal diseases. It is driven by retinal hypoxia frequently caused by capillary non-perfusion and endothelial cell (EC) loss. We investigated the role of EC apoptosis in this process using a mouse model of ischemic retinopathy, in which vessel closure and EC apoptosis cause capillary regression and retinal ischemia followed by neovascularisation. Protecting ECs from apoptosis in this model did not prevent capillary closure or retinal ischemia. Nonetheless, it prevented the clearance of ECs from closed capillaries, delaying vessel regression and allowing ECs to persist in clusters throughout the ischemic zone. In response to hypoxia, these preserved ECs underwent a vessel sprouting response and rapidly reassembled into a functional vascular network. This alleviated retinal hypoxia, preventing subsequent pathogenic neovascularisation. Vessel reassembly was not limited by VEGFA neutralisation, suggesting it was not dependent on the excess VEGFA produced by the ischemic retina. Neutralisation of ANG2 did not prevent vessel reassembly, but did impair subsequent angiogenic expansion of the reassembled vessels. Blockade of EC apoptosis may promote ischemic tissue re-vascularisation by preserving ECs within ischemic tissue that retain the capacity to reassemble a functional network and rapidly restore blood supply.
Publisher
ASCI
Research Division(s)
Advanced Technology And Biology; Epigenetics And Development
PubMed ID
32427589
NHMRC Grants
NHMRC/1125536NHMRC/110100891
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-05-25 01:54:58
Last Modified: 2020-05-25 01:59:25
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