Glycobiology of ocular angiogenesis

Abstract

Ocular neovascularization can affect almost all the tissues of the eye: the cornea, the iris, the retina, and the choroid. Pathological neovascularization is the underlying cause of vision loss in common ocular conditions such as diabetic retinopathy, retinopathy of prematurity and age-related macular neovascularization. Glycosylation is the most common covalent posttranslational modification of proteins in mammalian cells. A growing body of evidence demonstrates that glycosylation influences the process of angiogenesis and impacts activation, proliferation, and migration of endothelial cells as well as the interaction of angiogenic endothelial cells with other cell types necessary to form blood vessels. Recent studies have provided evidence that members of the galectin class of β-galactoside-binding proteins modulate angiogenesis by novel carbohydrate-based recognition systems involving interactions between glycans of angiogenic cell surface receptors and galectins. This review discusses the significance of glycosylation and the role of galectins in the pathogenesis of ocular neovascularization.

Keywords: angiogenesis; choroidal neovascularization; corneal neovascularization; galectin-3; glycans; glycosylation; integrins; neovascularization; retinal neovascularization.

Fig. 1.

Schematic and photographic representation of the eye and corneal, retinal, and CNV. (A) Schematic depiction of the eye. (B) The fundus, i.e., the inner lining of a normal eye. (C and D) Normal cornea is transparent and avascular; in response to trauma, graft rejection or infection, blood vessels from the limbus (region where transparent cornea meets the opaque sclera) invade the cornea. (E and F) The retina is a highly ordered, multilayered structure that is richly vascularized. Diabetic retinopathy can lead to ischemia and neovascularization on the surface of the retina. (G and H) AMD can be associated with subretinal neovascularization originating from the choriocapillaris, and this can lead to subretinal hemorrhage. Credit: (A), (E) and (G) downloaded from National Eye Institute, NIH website with permission (ref.: NEA04, EDA01, EDA 24); (B) provided by J. S. Duker; (C) provided by Sugaya Satoshi and Tohru Sakimoto; (F) and (H) from Friedlander (2007) with permission.