Twenty patients with age-related macular degeneration, an absolute central scotoma and a mean visual acuity of 0.04 (20/475) were studied. A scanning laser ophthalmoscope (SLO) was used for microperimetry and determination of preferred retinal locus, often located to the left of the retinal lesion (corresponding to a location to the left of the visual field scotoma), which is considered unfavorable for reading. All 20 patients were trained to use a new and more favorable retinal locus for reading, above (or occasionally below) the retinal lesion (corresponding to a location below or above the visual field scotoma), first by reading scrolled text under simultaneous fixation monitoring and instruction in the SLO and then by reading printed text, using high magnification (mean 14.3x). For the 18 patients who learned to use eccentric viewing, reading speed with adequate magnification prior to training was 9.0+/-5.8 words/min. With training (mean 5.2 hours), it increased significantly (p<0.001) to 68.3+/-19.4 words per min. Training of eccentric reading has thus proved to be very successful.

H(2)DCF-DA (dihydrodichlorofluorescein diacetate) is widely used to evaluate 'cellular oxidative stress'. After passing through the plasma membrane, this lipophilic and non-fluorescent compound is de-esterified to a hydrophilic alcohol [H(2)DCF (dihydrodichlorofluorescein)] that may be oxidized to fluorescent DCF (2',7'-dichlorofluorescein) by a process usually considered to involve ROS (reactive oxygen species). It is, however, not always recognized that, being a hydrophilic molecule, H(2)DCF does not cross membranes, except for the outer fenestrated mitochondrial ones. It is also not generally realized that oxidation of H(2)DCF is dependent either on Fenton-type reactions or on unspecific enzymatic oxidation by cytochrome c, for neither superoxide, nor H(2)O(2), directly oxidizes H(2)DCF. Consequently, oxidation of H(2)DCF requires the presence of either cytochrome c or of both redox-active transition metals and H(2)O(2). Redox-active metals exist mainly within lysosomes, whereas cytochrome c resides bound to the outer side of the inner mitochondrial membrane. Following exposure to H(2)DCF-DA, weak mitochondrial fluorescence was found in both the oxidation-resistant ARPE-19 cells and the much more sensitive J774 cells. This fluorescence was only marginally enhanced following short exposure to H(2)O(2), showing that by itself it is unable to oxidize H(2)DCF. Cells that were either exposed to the lysosomotropic detergent MSDH (O-methylserine dodecylamide hydrochloride), exposed to prolonged oxidative stress, or spontaneously apoptotic showed lysosomal permeabilization and strong DCF-induced fluorescence. The results suggest that DCF-dependent fluorescence largely reflects relocation to the cytosol of lysosomal iron and/or mitochondrial cytochrome c.

Earlier we identified an Immune Risk Profile (IRP) of very old individuals, 86-94 years of age, characterised by an inverted CD4/CD8 ratio and associated with persistent cytomegalovirus infection and an increase in the numbers of CD3+CD8+CD28- cells. In the present study we included data from a population-based sample in the age range of 20-79 years to examine the prevalence of individuals with an inverted CD4/CD8 ratio relative to age and gender across the entire adult lifespan. Immunological monitoring that was conducted included analysis of the numbers of T-cells in the subsets CD3+, CD3+CD4+, and CD3+CD8+ as well as CD3+CD8+CD28+, CD3+CD8+CD28-, and CD8+CD45RA+CCR7+. There was found to be a significant lowering of the numbers of CD3+, CD3+CD4+, and CD3+CD8+, and of the CD8+CD45RA+CCR7+ cells across the adult life-span. Notably, the prevalence of individuals with an inverted CD4/CD8 ratio increased from about 8% in the age range of 20-59 years to about 16% in the age range of 60-94 years. The mortality rate in individuals with an inverted CD4/CD8 ratio also increased significantly above the age of 60. Interestingly, the proportion of individuals with an inverted CD4/CD8 ratio was found to be significantly higher in men, whereas the numbers of CD3+CD4+ helper and CD8+CD45RA+CCR7+ naïve cells and the CD4/CD8 ratio were found to be significantly higher in women. These results highlight the importance of functioning of the thymus in the development of IRP and may partly account for the differences between sexes in terms of longevity.

it is concluded that comorbidity of diabetes and hypertension produce a pronounced cognitive decline. This finding emphasises the importance of prevention and treatment of those highly prevalent diseases in the old population.

We examined change in neuropsychological test performance related to type 2 diabetes mellitus across a 6-year interval. A population-based sample of 274 elderly participants (36 with diabetes and 238 without diabetes) was examined at four occasions at a 2-year interval. The participants were 80-93 years of age (M = 82.8 years) and without dementia at baseline. The test battery included tests of speed, visuospatial ability, short-term memory, semantic memory, episodic memory, and the Mini Mental Status Examination. Several models, taking into account diabetes and demographic data, were analyzed using SAS Proc Mixed multilevel modeling. At baseline, there were no significant differences in the neuropsychological tests related to diabetes. The longitudinal analyses, however, showed that diabetes was a significant predictor of decline for many of the tests. These findings points to the conclusion that type 2 diabetes is associated with accelerated cognitive decline in old age that may result in dementia.