Comparative Study Of Post-natal Retinal Vascular Development In Mice Models Of iPLA2 Inhibition And Plasmalogen Deficiency

Abstract

Purpose: : Plasmalogens are particular phospholipids characterized by the presence of a vinyl-ether bond and of a polyunsaturated fatty acid (PUFA) at sn-1 and sn-2 positions of glycerol, respectively. Even if the plasmalogen content of organs and tissues is well documented, their biological functions are still enigmatic. Plasmalogen deficiency in DAPAT^-/- mice leads to developmental abnormalities in retinal vasculature (Acar et al, ARVO 2007 E-Abstract 2978) and to persistent hyaloïd arteries. We hypothesize that plasmalogens regulate retinal vascular development through the liberation of PUFA by a plasmalogen-specific calcium-independent phospholipase A2 (iPLA2). We have performed a comparative study of the retinal vascular development in mouse models of iPLA2 inhibition in comparison to total plasmalogen-deficiency.

Methods: : Retinal vascular development was studied at P7, P14 and P21 on flat mounted retina taken from DAPAT+/+ and DAPAT-/- mice and from C57BL/6 mice treated or not with the iPLA2 inhibitor, bromoenol lactone (BEL). Isolectin B4 was used to stain retinal endothelial cells whereas the astrocyte network was visualized after GFAP immunostaining. Pericytes and fibronectin influence on vascular development was evaluated by anti-NG2 Chondroitin sulfate proteoglycan and anti-fibronectin antibodies, respectively.

Results: : Similar abnormalities in retinal vascular development were observed in DAPAT-/- mice and C57BL/6 mice treated with BEL. These consisted in an increased number of vessel ramifications and abnormal presence of glial cells in retina at P14. We have observed an abnormal migration of glial cells from the optic nerve at P21, and a large number of activated microglial cells in adult mice.

Conclusions: : Our study consistently highlights the role of plasmalogen-specific iPLA2, and subsequent release of PUFA from the sn-2 position of plasmalogens, in the development of retinal vessels.

Keywords: lipids • development • retinal neovascularization