Abstract
Purpose :
Our previous work described so called labyrinth capillaries (LC) as a possible source of leakage in surgically excised choroidal neovascular (CNV) membranes: the leakage was caused by capillaries with open cellular junctions, but more importantly, these vessels also showed microvillar projections into the vessel lumen which blocked cellular perfusion while allowing unhamperered flow of plasma (Schraermeyer et al., 2015, doi: 10.1007/s00417-014-2733-0). The LCs were proposed to be responsible for the permanent leakage of fluid in AMD and therefore merit awareness. Early stages of LCs, like microvillar processes of endothelial cells into the vessel lumen were coincidently observed in our neovascular disease models after VEGF overload or induction of hypoxia. They are described for the first time in this work.
Methods :
Endothelial alterations of the choriocapillaris and CNV vessels were ultrastructurally investigated in plastic sections of surgically excised CNV membranes and compared to the following models: CNV induced by viral VEGF overexpression in 1) rats and 2) rabbits, 3) CNV induced by subretinal VEGF protein injection in rats, 4) rat eyes after exposure to hypoxia.
Results :
Early signs of LC formation were found in all groups investigated and showed the following features: irregular structure of endothelial cells leading to formation of microvillar processes into the vessel lumen. The processes regularly grew into bridging connections to neighbouring endothelial cells forming new internal lumina. If choriocapillaris was involved, those bridges also contained fenestrations. Already after VEGF challenge for one day, endothelial cells were highly activated and showed luminal microvillar projections and endothelial gaps. Only in the human excised CNV membranes and the rabbit VEGF overexpression model, fully grown labyrinth capillaries were observed.
Conclusions :
Here we show that experimental challenge with VEGF or hypoxia can lead to formation of labyrinth capillaries in the choroid in four different model systems. These models can be used to study new drugs to inhibit the formation of leaky capillaries in wet AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.