Ether-Lipids Are Involved in Retinal Vegf Expression and in Postnatal Hyaloid Vessel Regression

Abstract

Purpose: : Ether-lipids are phospholipids that represent about 13% of retinal lipids and whose exact functions remain unknown. However, the preferential esterification of polyunsaturated fatty acids (PUFAs) at the sn-2 position of ether-lipids and their liberation by an ether-lipid-specific phospholipase A2 suggest their involvement in cell signaling processes. Based on the data showing the persistence of the hyaloid vasculature in ether-lipid-deficient mice (DAPAT^-/- mice, Rodemer et al Hum Mol Genet 2003), we further investigated the molecular mechanisms by which ether-lipids may regulate hyaloid vessels regression during post-natal development.

Methods: : C57BL/6 mice were treated at birth either with a saline solution or with an inhibitor of the 39kDa-ether-lipid-specific phospholipase A2 (BEL, bromoenol lactone). The hyaloid vasculature, represented by hyaloid arteries (HA) and vasa hyaloidea propria (VHP) vessels, was monitored by means of fluorescein angiography with a confocal SLO (Heidelberg Retina Angiograph, Heidelberg Engineering) from postnatal day (PN) 17 to 54. The retinal expression of VEGF isoforms was measured by quantitative PCR at PN21 and PN56.

Results: : HA were present in the vitreous of all animals at PN35 but not at PN54. Animals treated with BEL displayed a delayed regression of HA since they had a significantly higher number of HA in their vitreous when compared to controls until PN35 (means of 2.90 ± 0.56 vs 1.62 ± 0.51 at PN35, respectively). VHP vessels completely regressed in control animals at PN27 whereas they were still present at PN35 in mice treated with BEL. No VHP vessel was observed at PN54 in any mouse treated with BEL. VEGF₁₂₀ and VEGF₁₆₄ were over-expressed in BEL-treated mice at PN21 but not at PN56. A similar over-expression of VEGF₁₂₀ and VEGF₁₆₄ was observed in adult DAPAT^-/- mice.

Conclusions: : Ether-lipids may be involved in the regression of the hyaloid vasculature during post-natal development. Our results suggest that this regulation involves the liberation of PUFAs esterified at the sn-2 position of ether-lipids and their potential action on the genetic expression of angiogenic factors.

Keywords: lipids • vascular endothelial growth factor • development