Age-related changes of cystatin C and effects on protein turnover in RPE cells

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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.
Original languageEnglish
Number of pages1
JournalActa Ophthalmologica
Issue numberS256
Publication statusPublished - 14 Sept 2016


  • Ophthalmology


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