heparitin-sulfate and Retinal-Neovascularization

Loss of vitreal transparency is common to many forms of visual impairment. Examples include bleeding from retinal neovascularization and presence of intraocular inflammation. To treat the vitreous opacity, it is essential to explore the pathology of each underlying disease. However, understanding the mechanisms of vitreous transparency is also important. This review shows that the vitreous contains a high concentration of soluble heparan sulfate, a glucosaminoglycan (sugar chain). This inhibits the aberrant growth of retinal vessels into the vitreous by inactivating the heparin-binding protein, the vascular endothelial growth factor (VEGF), that is secreted into the vitreous. In addition, the possibilities that intraocular soluble glucosaminoglycans can inhibit the function of another heparin-binding inflammatory cytokine, CCL2, and suppress the intraocular inflammation, are proposed. Thus, intravitreal glucosaminoglycan may serve as a common inhibitor of various heparin-binding proteins including VEGF and CCL2. The results suggest that sugar chains regulate the signaling of these proteins and suppress the intravitreal infiltration of vascular endothelial cells and inflammatory cells, contributing to the maintenance of vitreal transparency.

Topics: Antimicrobial Cationic Peptides; Blood Proteins; Carrier Proteins; Glycosaminoglycans; Heparitin Sulfate; Humans; Retinal Neovascularization; Retinal Vessels; Signal Transduction

Basic fibroblast growth factor (FGF) is a potent endothelial cell mitogen that has been proposed to play a role in proliferative diabetic retinopathy and other neovascular processes. Our understanding of the in vivo role of basic FGF in the pathogenesis of these disorders is limited. We studied the immunolocalization of basic FGF in 16 clinical cases of diabetic retinopathy to determine whether the normal retinal distribution of basic FGF changed during the development of diabetic retinopathy and correlated with the onset of retinal neovascularization. By using monoclonal and affinity-purified polyclonal antibodies against basic FGF and heparan sulfate proteoglycan (HSPG), we found that basic FGF colocalized with HSPG to vascular basement membranes. As the basement membranes thickened during the progression of diabetic retinopathy, the intraretinal stores of immunoreactive basic FGF and HSPG expanded. With the development of neovascularization, the colocalization of basic FGF and HSPG changed; HSPG localized to basement membranes, while basic FGF localized intracellularly, with only minimal basement membrane immunoreactivity. Incubations of the neovascular fronds with exogenous basic FGF demonstrated multiple HSPG glycosaminoglycan-binding sites for basic FGF, indicating that basic FGF had not been released from the matrix of neovascular fronds by heparitanase digestion.

Topics: Antibodies, Monoclonal; Basement Membrane; Chondroitin Sulfate Proteoglycans; Diabetic Retinopathy; Fibroblast Growth Factors; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Immunoenzyme Techniques; Polysaccharide-Lyases; Retina; Retinal Neovascularization