Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium.
Vis Neurosci
; 30(3): 55-64, 2013 May.
Article
in En
| MEDLINE
| ID: mdl-23611523
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retina
/
Carrier Proteins
/
Cathepsin D
/
Retinal Pigment Epithelium
Limits:
Animals
Language:
En
Journal:
Vis Neurosci
Journal subject:
NEUROLOGIA
/
OFTALMOLOGIA
Year:
2013
Type:
Article
Affiliation country:
United States