Loss of Melanoregulin (MREG) Enhances Cathepsin-D Secretion by the Retinal Pigment Epithelium

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Departmental Papers (Dental)
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Retinal pigment epithelium
Cathepsin-D processing
Phagocytosis
Protease secretion
Dentistry
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Frost, Laura S.
Lopes, Vanda S.
Stefano, Frank F.
Bragin, Alvina
Williams, David S.
Mitchell, Claire H.
Boesze-Battaglia, Kathleen
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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 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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2013-05-01
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Visual Neuroscience
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