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Age‐related changes of cystatin C and effects on protein turnover in RPE cells
Author(s) -
Paraoan L.
Publication year - 2016
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2016.0166
Subject(s) - cystatin c , cystatin , proteolysis , secretion , choroid , glycation , retinal pigment epithelium , microbiology and biotechnology , macular degeneration , intracellular , retina , biology , chemistry , biochemistry , retinal , medicine , enzyme , neuroscience , receptor , renal function , ophthalmology
Summary Essential functions of the retinal pigment epithelium (RPE) rely on specific proteolysis processes that require efficient regulation both intra‐ and extracellularly. One of the most potent regulators of proteolysis, the cysteine proteinase inhibitor cystatin C, is among the top 2% abundantly expressed genes by RPE. The secretion profile of cystatin C in RPE cells suggests a role in relation to maintaining the structure and function of Bruch's membrane/choroid. Variant B cystatin C is associated with increased risk of developing exudative age‐related macular degeneration (AMD) and presents leader sequence‐related altered intracellular trafficking, leading to reduced efficiency of processing through the secretory pathway. The abundance of cystatin C is reduced with ageing in the macula region of the RPE/choroid and cystatin C expression and secretion are significantly decreased in response to the accumulation of advanced glycation end‐products (AGEs). Together the data point out to a likely role for the wild type cystatin C in regulating the proteolytic homeostasis in the retina/choroid, which is declining with age and the decline is accelerated in homozygous carriers of AMD‐associated variant B.