Developmental Expression of VLDL Receptor in the Retinal Pigment Epithelium and Photoreceptor

Abstract

Purpose: : Our previous studies have shown that VLDL receptor is a potent endogenous inhibitor negatively regulating retinal vascular endothelial cells (RVECs) and that VLDLR knockout does not alter the early postnatal development of retinal vasculature. This study examines the expression of VLDLR in non-vascular cells in the retina during the development.

Methods: : C57BL6 mice at different developmental ages were used for the study. The level and cellular origin of VLDLR expression in the mouse retina during postnatal development were determined by immunofluorescent staining. Cellular distribution of VLDLR was examined in isolated photoreceptors and RPEs by immunofluorescent staining or double labeling with ZO-1 or RGR antibody.

Results: : No specific staining of VLDLR was detected in the retina at postnatal day 2 (P2). The expression of VLDLR protein in RPEs was first detectable at P6. The staining intensity became much stronger at P10. In addition, strong signals were noticeable in the outer edge of the photoreceptor cell body layer corresponding to newly developed inner segments of photoreceptors at P10. The expression of VLDLR in both RPE and PR remained intense through P15, P20 to adult. Immunocytochemistry staining in isolated RPE whole mount showed that VLDLR expression was primarily concentrated in the basal membrane of RPE. VLDLR staining pattern had minimal co-localization with ZO-1 antibody. Staining of isolated photoreceptors indicated VLDLR was localized in the inner segment of PR. The onset of VLDLR expression in these non-vascular cells in the outer retina corresponds to the late stage of retinal vessel development.

Conclusions: : The onset of VLDLR expression in the outer retina at the end of the second postnatal week in mice is correlated with later stage of retinal vessel development while forming the two deep layers of capillary beds in the inner and outer plexiform layers. VLDLR expression in the outer retina might be important signals preserving avascular zone in the photoreceptor layer.

Keywords: age-related macular degeneration • neovascularization • retinal pigment epithelium