Age-related HS changes have implications for AMD

Researchers examining age-related changes in heparan sulphate (HS) quantity and composition in human Bruch's membrane (BrM) have discovered that the quantity greatly decreases with age, resulting in fewer binding sites for complement factor H (CFH) and affecting the ability of the 402H variant of CFH to bind BrM. Their findings, published in Investigative Ophthalmology and Visual Science, are important because HS and age-related macular degeneration (AMD) have been linked; HS is the primary binding partner for CFH in human BrM, and CFH plays a main part in the prevention of complement activation on extracellular matrices.

The Manchester, UK, investigators examined ocular tissue from deceased humans believed not to have had retinal disease. They discovered through disaccharide analysis that the mean quantity of HS in BrM was 50% lower in old donors (average age, 82 years) compared with young donors (average age, 32 years). Also, the researchers noted a small but significant decrease in HS sulphation in old BrM.

Through immunohistochemistry, they saw approximately 50% less HS in macular BrM in the older donors compared with the younger ones. Heparanase-1 increased by 24% in the old macular BrM. In the ocular tissue from the young donors, the 402H CCP6-8 60 associated with AMD bound ‘relatively poorly’ to BrM compared with the 402Y form, the authors noted. The difference was more pronounced in BrM from the older donors, they added.

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