Ether-Lipid-Deficient-Mice Display Pigmentary Glaucoma Features as Well as Abnormal Retinal Vasculature

Abstract

Purpose:: Ether-lipids are a phospholipid subclass representing about 13% of retinal lipids. Although antioxidant properties were attributed to them, their exact functions remain unknown, especially in the eye. Persistent hyaloid arteries, cataract and iris pigment dispersion have already been described in ether-lipid-deficient mice (DAPAT^-/- mice, Rodemer et al Hum Mol Genet 2003). We further investigated the ocular phenotype of DAPAT^-/- mice with a particular attention to intra-ocular pressure (IOP), retinal function, oxidative stress and vasculature.

Methods:: Adult DAPAT^-/- mice and C57BL/6 controls were used. The anterior eye was examined using a digital slit-lamp. IOP was measured with a hand-held tonometer (TonopenXL®). Scotopic and photopic electroretinograms (ERGs) were recorded according to ISCEV standards. Superoxide anion was localized in retinal sections by dihydroethidium (DHE) staining. Retinal vascularization was evaluated by confocal fluorescence microscopy on FITC-perfused whole-mounted retinas.

Results:: Central dense cataract was not generalized to all DAPAT^-/- eyes. Iris pigment dispersion was confirmed and was associated with elevated IOP (21.0 versus 17.5 mm Hg). ERGs were recorded in animals with light cataract only and revealed a specific alteration of the b-wave amplitude. A 20-fold increase in superoxide anion levels was observed in retinal ganglion cells of DAPAT^-/- mice by comparison to controls. Retinal vasculature revealed abnormal tortuous arteries and veins as well as higher density of retinal capillaries.

Conclusions:: Ether-lipids may be involved in the pathogenesis of pigmentary glaucoma as well as in retinal vascular development. However, it is unclear whether the increased retinal oxidative stress is the consequence of ether-lipid deficiency itself or that of elevated IOP.

Keywords: lipids • inner retina dysfunction: biochemistry and cell biology • oxidation/oxidative or free radical damage