Frost, Laura S.Lopes, Vanda S.Stefano, Frank P.Bragin, AlvinaWilliams, David S.Mitchell, Claire H.Boesze-Battaglia, Kathleen2023-05-222023-05-222013-05-012022-10-24https://repository.upenn.edu/handle/20.500.14332/9113Abstract 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. Copyright © Cambridge University Press, 2013.Cathepsin-D processing; Phagocytosis; Protease secretion; Retinal pigment epitheliumDentistryArticle