Hypoxia induces formation of leaky capillaries that resemble vessels in CNV

Session Details

Session Title: Free Paper Session 14: AMD IV

Session Date/Time: Friday 08/09/2017 | 16:30-18:00

Paper Time: 17:48

Venue: Room 111

First Author: : M.Tikhonovich RUSSIA

Co Author(s): :    A. Biesemeier   U. Schraermeyer                          

Abstract Details

Purpose:

ischaemia of the posterior eye chamber is one of the severe problems in ophthalmology. However, little is known about changes of existing fully formed choroidal blood vessels under ischaemic conditions. This study was based on a new model and it reports findings in the choroid of rats 14 hours after ischaemia.

Setting:

Division of Experimental Vitreoretinal Surgery, centre for Ophthalmology, Tübingen, Germany

Methods:

The study involved 16 adult six weeks old male rats (32 eyes). Eight pigmented and eight albino animals were used. ischaemia was modeled by incubating the eyes in PBS or DMEM at 4°C during fourteen hours after enucleation. Eyes fixed immediately after enucleation were used as a control. Transmission electron microscopy and immunohistochemical staining for HIF-1α and VEGF were performed. Statistical analysis was performed by using a nonparametric Mann-Whitney test.

Results:

Retinal and choroidal cells were still alive after 14 hours of incubation at 4°C and they showed an increase of HIF-1α and VEGF compared to the control. Due to ischaemia the endothelial cells of the choriocapillaris changed their morphology and made microvillar projections into the choriocapillaris lumen, which were often fenestrated. Because of the projections the area of the endothelial cell surface increased four (p<0.001) times and the length of the endothelial cell contour by 58% (p<0.001) in comparison to the control group. The endothelial cell projections tried to build up a new lumina inside the existing choriocapillars. In severe cases, the projections formed a labyrinth structure which nearly closed the vessel lumen. In addition, a lot of gaps between the endothelial cells were found. In the choroidal melanocytes of pigmented rats, a great number of degrading melanosomes were found after 14 hours of ischaemia.

Conclusions:

By using this easy, fast and cheap model of ischaemia the first steps of choroidal neovascularization (CNV) were shown: the increase of synthesis of HIF-1α and VEGF which is very likely responsible for the formation of gaps between endothelial cells and the formation of fenestrated endothelial cell projections into the vessel lumen. Their abundance can block perfusion of blood cells and thereby inhibit closure of the endothelial gaps by platelets, but still allow the flow of plasma. This may be the reason for a permanent leakage of fluid as it was found in so called labyrinth capillaries in surgically excised human CNV membranes before (DOI 10.1007/s00417-014-2733-0).

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