Journal
VISUAL NEUROSCIENCE
Volume 30, Issue 3, Pages 55-64Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0952523813000096
Keywords
Retinal pigment epithelium; Cathepsin-D processing; Phagocytosis; Protease secretion
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Funding
- NIH [R01 EY010420, R21EY018705, R01 EY013434]
- Vision Research Core Grant [EY001583]
- [R01 EY07042]
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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 Mreg(dsu/dsu) mouse, we observe increased basal laminin. Loss of the Mreg(dsu) 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.
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