Involvement of plasmalogens and iPLA2 in the control of post-natal retinal vascular development in mice

Abstract

Purpose: The correct development of retinal blood vessels is essential to ensure vision process through sufficient oxygen and nutrient supplies to the retina. It was shown that polyunsaturated fatty acids (PUFAs) could modulate factors involved in tissue vascularization. A congenital deficiency in ether-phospholipids also termed as “plasmalogens” was shown to lead to abnormal ocular vascularization. Because plasmalogens are considered as reservoirs of PUFAs, we wanted to better understand the mechanisms by which plasmalogens may regulate retinal vascular development through the release of PUFAs by a calcium-independent phospholipase A2 (iPLA2).

Methods: Retinal vascular development was followed in a mouse model of plasmalogen deficiency (DAPAT mice) as well as in a mouse model of retinal iPLA2 inhibition. Retinas were collected from birth until the age of 21 days. They were either flat-mounted and immuno-labelled to visualize the cells involved in vessel formation, or used to determine the expression of genes involved in inflammation and angiogenesis.

Results: The lack of plasmalogens was associated to defects in angiogenic processes during early phases of retinal vascular development. Particularly, the absence of plasmalogens influenced astroglial activity during the primary astrocyte template formation, promoted endothelial cell proliferation during sprouting angiogenesis, and impacted the expression of genes involved in angiopoietin/tie pathways. These early defects led to a disorganized and dysfunctional retinal vascular network at adult age. As mice in which iPLA2 was inhibited exhibited a similar vascular phenotype when compared to DAPAT mice, we suggest that these processes may be mediated by PUFA release from plasmalogens and further signalling through angiopoietin/tie pathways.

Conclusions: These data suggest a crucial role of plasmalogens during the formation of retinal vessels.

Keywords: 698 retinal development • 583 lipids • 429 astrocyte