Age-related increase in activity of specific lysosomal enzymes in the human retinal pigment epithelium

Abstract

Age related changes in the activity of lysosomal enzymes have been studied in the cultured human retinal pigment epithelium cells collected from 26-85 year old donors. Among four such enzymes studied, activities of cathepsin D and β-glucuronidase increased with the age of the donors while no notable change in activity of arylsulfatase B and α-mannosidase was observed. Kinetic parameters of β-glucuronidase was measured in retinal pigment epithelium cells isolated from donors of different ages. Similar kinetic parameters for β-glucuronidase at different ages suggest that the observed increase in the activity of the enzyme with age is not due to post- translational modification of the enzyme. Western blot analysis provides evidence for increased synthesis of β-glucuronidase with aging. Relative proportions of glycosaminoglycans, the natural substrates of β-glucuronidase and arylsulfatase B, in the retinal pigment epithelium altered with the age of the donors. A significant decrease of dermatan sulfate levels with aging correlates Well with the observed increase in the level of β-glucuronidase activity.