Significance of Hyaluronan in the Pathogenesis of Choroidal Neovascularization in Advanced Age-Related Macular Degeneration

Abstract

 

Purpose:

 

Hyaluronan (HA), a component of the extracellular matrix (ECM), is a large, non-sulfated glycosaminoglycan composed of repeats of two alternating sugar units, β-D-N-acetylglucosamine and β-D-glucuronate. Dynamic turnover of ECM is an important hallmark of tissue remodeling that occurs in advanced age-related macular degeneration (AMD). Recent studies have demonstrated that HA can induce inflammatory signals as well as angiogenesis. The role of HA in AMD is unknown. We hypothesized that HA metabolism may be altered in patients with advanced AMD.

 

Methods:

 

Serum was prepared from study volunteers that included 66 healthy control subjects and 49 patients with advanced AMD. Demographic and clinical characteristics of the donors were analyzed. Serum levels of hyaluronan were quantified by an HA-binding assay. Retina/choroid levels of hyaluronan were evaluated with fluorophore-assisted carbohydrate electrophoresis (FACE) assays as well as by immunohistochemistry using post-mortem control and AMD eyes.

 

Results:

 

Serum levels of HA were significantly elevated in patients with advanced AMD (choroidal neovascularization and geographic atrophy) 111.80 ± 27.2 ng/ml compared with normal controls, 32.91 ± 5.7ng/ml (p = 0.001). In contrast, in the retina/choroid, HA was significantly decreased in patients with GA and CNV when compared with normal controls.

 

Conclusions:

 

Hyaluronan is elevated in AMD serum and may have a critical role in the pathogenesis of advanced AMD. Elucidation of the roles of HA in various stages of AMD disease progression will generate novel insights into the pathophysiology of the disease.

 

Keywords: age-related macular degeneration • retinal degenerations: cell biology • proteoglycans/glycosaminoglycans