title: Distribution of cathepsin D in human eyes with or without age-related maculopathy.
abstract: Cathepsin D is a ubiquitous enzyme which plays an important role in the catabolism of proteins. Enzymatic studies showed that cathepsin D is the most important lysosomal enzyme in the proteolysis of opsin. The importance of cathepsin D in the lysosomal digestion of phagocytosed photoreceptor outer segments by the retinal pigment epithelium suggests that a decrease in cathepsin D activity might contribute to the development of hyalinized drusen and to the development of age-related maculopathy. The aim of this project was to study the immunohistochemical localization of cathepsin D in human eyes and particularly to compare the immunoreactivity of cathepsin D normal retinal pigment epithelial cells and in cells surrounding hyalinized drusen or lesions of age-related maculopathy. Following clinicopathological examinations the eyes were fixed, paraffin embedded and individual sections were subjected to Picro-Mallory staining for histopathological examination. Bleaching was performed then immunohistochemistry was carried out using a monoclonal mouse anti-human cathepsin D antibody. On the basis of the appearance of basal laminar deposit the eyes were divided into five groups corresponding to levels of progression in age-related maculopathy development. Following optimization of bleaching cathepsin D immunostaining was clearly visible in the iris epithelium, ciliary body and the retinal pigment epithelial layer of all eyes with the highest immunoreactivity present in the RPE cells. Within the neural retina the ganglion cells demonstrated a weak signal. Retinal pigment epithelial cathepsin D immunoreactivity was not impaired by age, geographical location or by age-related maculopathy status. There was a small increase in cathepsin D immunoreactivity around hyalinized drusen. The maintenance of cathepsin D immunoreactivity in eyes with hyalinized drusen or in samples with age-related maculopathy suggest that down-regulation of cathepsin D expression in the affected locations does not precede the development of these conditions. However, further studies are required to establish if the immunoreactive cathepsin D represents the fully processed biologically active enzyme.
authors.affiliation: Molecular Ophthalmology, Centre for Ophthalmology and Visual Science, University of Western Australia, Nedlands, Perth, Australia.
authors.forename: P E
authors.initials: PE
authors.lastname: Rakoczy
authors.forename: S H
authors.initials: SH
authors.lastname: Sarks
authors.forename: N
authors.initials: N
authors.lastname: Daw
authors.forename: I J
authors.initials: IJ
authors.lastname: Constable
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002402:Cathepsin D / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002924:Ciliary Body / Q000201:enzymology; D005123:Eye / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007498:Iris / Q000201:enzymology; D008268:Macular Degeneration / Q000201:enzymology*; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000201:enzymology; D015593:Retinal Drusen / Q000201:enzymology
chemical_list: D002402:Cathepsin D