Date of this Version
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.
This article has been published in a revised form in Visual Neuroscience [http://dx.doi.org/10.1017/S0952523813000096]. This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. © copyright holder.
Retinal pigment epithelium, Cathepsin-D processing, Phagocytosis, Protease secretion
Frost, L. S., Lopes, V. S., Stefano, F. F., Bragin, A., Williams, D. S., Mitchell, C. H., & Boesze-Battaglia, K. (2013). Loss of Melanoregulin (MREG) Enhances Cathepsin-D Secretion by the Retinal Pigment Epithelium. Visual Neuroscience, 30 (3), 55-64. http://dx.doi.org/10.1017/S0952523813000096
Date Posted: 01 March 2022
This document has been peer reviewed.