Dose dependency of irradiation on the transmission of blue light.

<p>The age (mean with range in parenthesis) of the donors used for the experiments is shown in the second column. The number of lenses used for each wavelength is shown in the third column and the number of lenses showing a significant dose-dependent increase in transmission as a function of increasing irradiation doses is shown in the fourth column.</p><p>The following columns show the result of modelling the photobleaching observations to the mathematical function: Trans_post = y0 + aTrans_pre + bDose^c. Trans_post is the transmission of blue light after irradiation and Trans_pre is the transmission of blue light before irradiation. The dose of irradiation was measured in J/cm². y0, a, b and c are constants. The constants are shown as parameter estimates with standard error of estimate in parenthesis. Only lenses showing a dose-dependent photobleaching effect were included in the modelling. RMSE: root mean square error.</p><p>Dose dependency of irradiation on the transmission of blue light.</p

Dose-dependency of photobleaching on the transmission of blue light computed using the mathematical expressions presented in Table 1 for a 75 year old lens for each of the six irradiation wavelengths used.

<p>Dose-dependency of photobleaching on the transmission of blue light computed using the mathematical expressions presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123732#pone.0123732.t001" target="_blank">Table 1</a> for a 75 year old lens for each of the six irradiation wavelengths used.</p

Comparison of blue light transmission before and after laser irradiation.

<p>The graph shows the transmission of blue light (450–490 nm) before (x-axis) and after (y-axis) laser irradiation at 375 nm (<b>△</b>), 405 nm (○), 420 nm (■), 445 nm (▲), 457 nm (×) and 473 nm (♦) for all 91 lenses included in the experiments.</p

Effect of irradiation wavelength on optical lens rejuvenation for a standard 75 year old lens.

<p>The photobleaching effect for each irradiation wavelength was calculated using the formulas presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123732#pone.0123732.t001" target="_blank">Table 1</a> using an irradiation dose of 4000 J/cm². The photobleaching effect was transformed into a clinically interpretable factor by calculating the apparent lens age after photobleaching using <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123732#pone.0123732.e001" target="_blank">Eq 1</a>. The numbers on the y-axis present the difference between the apparent lens age before and after irradiation. The photobleaching effect is presented as mean value (thick line), upper and lower 95% confidence intervals (thin hatched lines).</p

Transmission increase as a function of pre-treatment light absorption.

<p>The relationship between transmission of blue light before irradiation with the increase in transmission (in %) after transmission for each of the 6 different irradiation wavelengths used in the experiments. To facilitate comparison between different lenses the effect is normalized to an irradiation dose of 1000 J/cm² for all lenses.</p

Transmission changes after laser irradiation at 420 nm.

<p>The graph demonstrates the changes in transmission measured after irradiation by a 420 nm cw laser for a 68 year old human lens. From a baseline transmission that was lower than a 46-year old non-irradiated reference lens throughout the spectrum, transmission gradually increases to approach that of the younger reference lens after a dose of 1440 J/cm².</p

Retinal Adaptation to Changing Glycemic Levels in a Rat Model of Type 2 Diabetes

<div><h3>Purpose</h3><p>Glucose concentrations are elevated in retinal cells in undiagnosed and in undertreated diabetes. Studies of diabetic patients suggest that retinal function adapts, to some extent, to this increased supply of glucose. The aim of the present study was to examine such adaptation in a model of type 2 diabetes and assess how the retina responds to the subsequent institution of glycemic control.</p> <h3>Methods</h3><p>Electroretinography (ERG) was conducted on untreated Zucker diabetic fatty (ZDF) rats and congenic controls from 8–22 weeks of age and on ZDFs treated with daily insulin from 16–22 weeks of age. Retinal sections from various ages were prepared and compared histologically and by immunocytochemistry.</p> <h3>Principal Findings/Conclusions</h3><p>Acute hyperglycemia did not have an effect on control rats while chronic hyperglycemia in the ZDF was associated with scotopic ERG amplitudes which were up to 20% higher than those of age-matched controls. This change followed the onset of hyperglycemia with a delay of over one month, supporting that habituation to hyperglycemia is a slow process. When glycemia was lowered, an immediate decrease in ZDF photoreceptoral activity was induced as seen by a reduction in a-wave amplitudes and maximum slopes of about 30%. A direct effect of insulin on the ERG was unlikely since the expression of phosphorylated Akt kinase was not affected by treatment. The electrophysiological differences between untreated ZDFs and controls preceded an activation of Müller cells in the ZDFs (up-regulation of glial fibrillary acidic protein), which was attenuated by insulin treatment. There were otherwise no signs of cell death or morphological alterations in any of the experimental groups. These data show that under chronic hyperglycemia, the ZDF retina became abnormally sensitive to variations in substrate supply. In diabetes, a similar inability to cope with intensive glucose lowering could render the retina susceptible to damage.</p> </div

Effect of insulin on control Lean rat ERG.

<p>Units for intensity denoted as log cd*s/m²; Data presented are group mean ± SD; Amplitude denoted in µV; Implicit times (IT) denoted in ms; Age denoted in weeks.</p><p>Lean, congenic control rats; Lean-i, insulin treated Lean rats;</p>*<p>p<0.05; n = 8.</p

Number of animals examined by ERG for each time-point.

<p>ZDF, Zucker Diabetic Fatty rats; Lean, congenic control rats; ZDF-i, insulin treated ZDF.</p

Phosphorylated Akt (pAkt) immunofluorescence.

<p>A phospho-specific antibody was used to detect activated Akt in the retina of Lean (<b>a</b>), ZDF (<b>b</b>) and insulin treated ZDF (<b>c</b>) rats at 16 weeks of age; and of Lean (<b>d</b>), ZDF (<b>e</b>) and insulin treated ZDF (<b>f</b>) rats at 23 weeks of age. ZDF-i, insulin-treated ZDFs; ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer. Scale bar = 20 µm.</p