Normative contrast sensitivity values for the back-lit Melbourne Edge Test and the effect of visual impairment

Background: The Melbourne Edge Test (MET) is a portable forced-choice edge detection contrast sensitivity (CS) test. The original externally illuminated paper test has been superseded by a backlit version. The aim of this study was to establish normative values for age and to assess change with visual impairment. Method: The MET was administered to 168 people with normal vision (18-93 years old) and 93 patients with visual impairment (39-97 years old). Distance visual acuity (VA) was measured with a log MAR chart. Results: In those eyes without disease, MET CS was stable until the age of 50 years (23.8 ± .7 dB) after which it decreased at a rate of ≈1.5 dB per decade. Compared with normative values, people with low vision were found to have significantly reduced CS, which could not be totally accounted for by reduced VA. Conclusions: The MET provides a quick and easy measure of CS, which highlights a reduction in visual function that may not be detectable using VA measurements. © 2004 The College of Optometrists.

Effects of advanced glycation end-products (AGEs) on retinal pigment epithelial (RPE) cells lysosomal function:implications for age-related macular degeneration (AMD)

Purpose: RPE lysosomal dysfunction is a major contributor to AMD pathogenesis. Controlled activity of a major class of RPE proteinases, the cathepsins, is crucial in maintaining correct lysosomal function. Advanced glycation end-products (AGEs) accumulate in the Bruch’s membrane (BM) with age, impacting critical RPE functions and in turn, contributing to the development of AMD. The aim of this study was to assess the effect of AGEs on lysosomal function by analysing the expression, processing and activity of the cysteine proteinases cathepsins B, L and S, and the aspartic proteinase cathepsin D. Methods: ARPE-19 cells were cultured on AGE-containing BM mimics (matrigel) for 14 days and compared to untreated substrate. Expression levels and intracellular processing of cathepsins B, D, L and S, were assessed by qPCR and immunoblotting of cell lysates. Lysosomal activity was investigated using multiple activity assays specific to each of the analysed cathepsins. Statistical analysis was performed using the Student’s independent T-test. Results: AGE exposure produced a 36% decrease in cathepsin L activity when compared to non-treated controls (p=0.02, n= 3) although no significant changes were observed in protein expression/processing under these conditions. Both the pro and active forms of cathepsin S decreased by 40% (p=0.04) and 74% (p=0.004), respectively (n=3). In contrast, the active form of the cathepsin D increased by 125% (p=0.005, n= 4). However, no changes were observed in the activity levels of both cathepsins S and D. In addition, cathepsin B expression, processing and activity also remained unaltered following AGE exposure. Conclusions: AGEs accumulation in the extracellular matrix, a phenomenon associated with the natural aging process of the BM, attenuates the expression, intracellular processing and activity of specific lysosomal effectors. Altered enzymatic function may impair important lysosomal processes such as endocytosis, autophagy and phagocytosis of photoreceptor outer segments, each of which may influence the age-related dysfunction of the RPE and subsequently, AMD pathogenesis.