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T. Ogawa, S. Oltjen, S. Boylan, L. Hjelmeland; Expression of Cathepsin S in Young and Aging RPE/Choroid of the Mouse Eye . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2286.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Our laboratory has recently used microarray analysis to show a dramatic upregulation of cathepsin S in the aging mouse RPE/choroid. Cathepsin S has previously been reported to be expressed in the RPE where it may function in the digestion of rod outer segments. Methods: Mouse eyes from 6 week old C57/B6, 24 month old C57/B6, and 12 week C57/B6 albino mice were fixed overnight at 4 °C in 4%paraformaldehye after which the posterior pole was dissected and embedded in OCT. Frozen sections were either subjected to in situ hybridization using a 1170 bp riboprobe from the 3’ end of the mouse cathepsin S transcript, or subjected to immunohistochemistriy using an antipeptide antibody (Santa Cruz) raised against an amino acid sequence near the carboxy terminus of the protein. Labeling for both in situ and immunohistochemistry was visualized using alkaline phosphatase with NBT/BCIP as a substrate. Pigmented eyes were bleached using 0.1 % K permanganate for 35 minutes followed by 5 minutes in 0.5% oxalic acid. Results: In whole sections of posterior pole, the most dramatic labeling for cathepsin S was observed in the ganglion cell layer both by in situ hybridization and immunohistochemistry. Much weaker staining was observed in RPE cells for RNA and protein, and the pattern was non-uniform with labeled cells occurring in clusters in an individual region. The number of labeled cells appeared to increase as a function of age, but this observation has not yet been demonstrated with statistical confidence. Conclusions: Although the role of cathepsin S in RPE cells has been proposed to be the digestion of ROS, studies from elsewhere in the CNS indicate alternate functions related to aging and pathology. Cathepsin S is clearly involved in the processing of Alzheimer Precursor Protein to the beta-amyloid peptide, and the expression of cathepsin S appears to be enhanced in regions of Alzheimer brains exhibiting advanced pathology. We speculate that cathepsin S may have some role in the thickening of Bruch’s membrane or the production of drusen in the aging eye.
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