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- Title
Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium.
- Authors
FROST, LAURA S.; LOPES, VANDA S.; STEFANO, FRANK P.; BRAGIN, ALVINA; WILLIAMS, DAVID S.; MITCHELL, CLAIRE H.; BOESZE-BATTAGLIA, KATHLEEN
- Abstract
Cathepsin-D (Cat-D) is a major proteolytic enzyme in phagocytic cells. In the retinal pigment epithelium (RPE), it is responsible for the daily degradation of photoreceptor outer segments (POSs) to maintain retinal homeostasis. Melanoregulin (MREG)-mediated loss of phagocytic capacity has been linked to diminished intracellular Cat-D activity. Here, we demonstrate that loss of MREG enhances the secretion of intermediate Cat-D (48 kDa), resulting in a net enhancement of extracellular Cat-D activity. These results suggest that MREG is required to maintain Cat-D homeostasis in the RPE and likely plays a protective role in retinal health. In this regard, in the Mregdsu/dsu mouse, we observe increased basal laminin. Loss of the Mregdsu allele is not lethal and therefore leads to slow age-dependent changes in the RPE. Thus, we propose that this model will allow us to study potential dysregulatory functions of Cat-D in retinal disease.
- Publication
Visual Neuroscience, 2013, Vol 30, Issue 3, p55
- ISSN
0952-5238
- Publication type
Article
- DOI
10.1017/S0952523813000096