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Luminita I. Paraoan, Donna Gray, Ian Grierson, Yit C. Yang, Simon Harding, Paul Hiscott; Characterisation of Cystatin C Expression in Human Retinal Pigment Epithelium in Relation to Age. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2340.
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The aim of this study was to investigate the temporal and spatial expression of the cysteine proteinase inhibitor cystatin C in situ in human retinal pigment epithelium (RPE) in relation to age.
The immunohistochemical study made use of eyes from 35 human donors, 16 of which were ≤ 65 years old and 19 >65 years old (age range 17 to 95 years old). Pigment bleaching was performed prior to incubation with anti-cystatin C antibody. Intensity of cystatin C immunoreactivity was evaluated with ImageJ software, taking uniformly calibrated greyscale measurements in three fields of each area analysed. Scatter plots of mean segmental grey values versus donor age were produced. Regression coefficients of the trendlines (r2) were used to assess statistical significance.
Cystatin C immunoreactivity in RPE was detected in all specimens with grades of intensity affected by the anatomical localisation of the RPE. Expression/accumulation levels of cystatin C were consistently higher in the posterior compared with the peripheral segment of RPE (p<0.01). Moreover, cystatin C expression levels showed a statistically significant decrease with age in the posterior RPE, but not in the peripheral segments of RPE (r2 values 0.120, respectively 0.002, with a critical r2 value of 0.111 for p=0.05). Preferential basal accumulation of cystatin C was also evident, consistent with its basolateral secretion demonstrated previously.
Our results suggest that a significant reduction of cystatin C level with age occurs in the posterior RPE. The findings highlight a compounding factor to the deleterious effects of variant B cystatin C in ageing RPE, which has been previously associated with increased risk of development of exudative age-related macular degeneration (AMD). Decreased cystatin C basolateral secretion may contribute to an altered proteolytic profile involved in ageing of the RPE and AMD.
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