Salvianolic acid B inhibits myofibroblast transdifferentiation in experimental pulmonary fibrosis via the up-regulation of Nrf2.

Salvianolic acid B (SalB) is one of the most bioactive components extracted from Salvia miltiorrhiza, and its antioxidant capacity corresponds with its protective effects against cell injury from oxidative stress. The aim of the present study was to evaluate the effect of SalB on experimental pulmonary fibrosis and its ability to ameliorate the oxidative/antioxidative imbalance during fibrosis pathogenesis. The anti-fibrotic activity of SalB was first confirmed in Transforming growth factor ß1(TGF-ß1)-stimulated MRC-5 cells. The protection of SalB against oxidative stress during fibrogenesis in vitro was verified by detecting ROS production, the levels of glutathione (GSH) and malondialdehyde (MDA). The Western blot and PCR results indicated that SalB could up-regulate nuclear factor erythroid-derived 2-like 2 (Nrf2) at both the protein and mRNA levels and induce Nrf2 nuclear translocation in vitro, which may be the mechanism underlying the anti-fibrotic capacity of SalB. Furthermore, the anti-fibrotic and antioxidant capacities of SalB in vivo were confirmed in rats with BLM-induced pulmonary fibrosis. The immunohistochemistry results showed that Nrf2 was absent in fibroblastic foci (FF) areas, while the SalB treatment could increase the expression of Nrf2 in lung tissues, especially in FF areas.

Variability and Errors of Manually Digitized Goldmann Visual Fields.

PURPOSE: Goldmann visual fields (GVFs) are useful for tracking changes in areas of functional retina, including the periphery, in inherited retinal degeneration patients. Quantitative GVF analysis requires digitization of the chart coordinates for the main axes and isopter points marked by the GVF operator during testing. This study investigated inter- and intra-digitizer variability among users of a manual GVF digitization program. METHODS: Ten digitizers were trained for 1 hour, then digitized 23 different GVFs from inherited retinal degeneration patients in each of three testing blocks. Digitizers labeled each isopter as seeing or non-seeing, and its target size. Isopters with the same test target within each GVF were grouped to create isopter groups. RESULTS: The standard deviation of isopter group area showed an approximate square-root relationship with total isopter group area. Accordingly, the coefficient of variation for isopter group area decreased from 68% to 0.2% with increasing isopter group area. A bootstrap version of ANOVA did not reveal a significant effect of digitizers on isopter group area. Simulations involving random sampling of digitizers showed that five to seven digitizers would be required to catch 95% to 99% of labeling errors and isopter misses, on the basis of data discrepancies, with 99% probability. CONCLUSIONS: These data suggest that any minimally trained digitizer would be capable of reliably determining any isopter area, regardless of size. Studies using this software could either use five to seven minimally trained digitizers for each GVF, three digitizers who demonstrate low frequencies of errors on a practice set of GVFs, or two digitizers with an expert reader to adjudicate discrepancies and catch errors.

Virtual wayfinding using simulated prosthetic vision in gaze-locked viewing.

PURPOSE: To assess virtual maze navigation performance with simulated prosthetic vision in gaze-locked viewing, under the conditions of varying luminance contrast, background noise, and phosphene dropout. METHODS: Four normally sighted subjects performed virtual maze navigation using simulated prosthetic vision in gaze-locked viewing, under five conditions of luminance contrast, background noise, and phosphene dropout. Navigation performance was measured as the time required to traverse a 10-room maze using a game controller, and the number of errors made during the trip. RESULTS: Navigation performance time (1) became stable after 6 to 10 trials, (2) remained similar on average at luminance contrast of 68% and 16% but had greater variation at 16%, (3) was not significantly affected by background noise, and (4) increased by 40% when 30% of phosphenes were removed. Navigation performance time and number of errors were significantly and positively correlated. CONCLUSIONS: Assuming that the simulated gaze-locked viewing conditions are extended to implant wearers, such prosthetic vision can be helpful for wayfinding in simple mobility tasks, though phosphene dropout may interfere with performance.

Real and virtual mobility performance in simulated prosthetic vision.

Wayfinding is an important activity that can be performed with limited visual resources, and thus may be an important application of early visual prostheses. In a pair of experiments we explored minimal visual resolution requirements of a simulated retinal electrode array for mobility in real and virtual environments, experienced by normally sighted subjects in video headsets. In experiment 1, inexperienced and experienced subjects traveled similar routes around a suite of offices with simulated implants of 4 x 4, 6 x 10 and 16 x 16 dots. In experiment 2, the effects of adding dynamic noise and removing a subset of 'phosphenes' from a 6 x 10 dot array on the mobility of experienced subjects through a series of different virtual 10-room buildings were determined. Performance was quantified in terms of time and navigation errors in both experiments, and wall contacts in the real environment; a compound score was also computed for trials in experiment 1. In experiment 1, inexperienced subjects required 16 x 16 dots for adequate performance, while experienced subjects reached similar levels with 6 x 10 dots. In experiment 2, dot removal up to 30% led to modest yet significant performance deterioration, and noise addition to slight but non-significant improvement, while practice led to a reduction in travel time by 50% over the 28-trial experiment. Error counts in experiment 2 were fairly high, but largely randomly distributed, and attributable to the high risk of becoming disoriented in the sparse visual environment. Substantial performance level differences were found between subjects, spanning a threefold range even after practice. The findings suggest that a retinal implant with as few as 60 electrodes may provide independent wayfinding abilities to the adventitiously blind, but that substantial practice and supervision will be required in learning this task.

Initiation and stability of pursuit eye movements in simulated retinal prosthesis at different implant locations.

PURPOSE: To assess the possible effects of retinal prosthesis implant location on the initiation and stability of pursuit eye movements. METHODS: Six normally sighted subjects visually tracked a horizontally moving target in natural vision and in simulated prosthetic vision. Subjects were instructed to press a key when the target jumped. Prosthetic vision was simulated with a 10 x 10 array of 1 degrees diameter phosphenes. Three implant locations in the retina were simulated: macular, 8 degrees superior, and 8 degrees nasal. Target motion had two speeds: 4 degrees /s and 8 degrees /s. Eye movement latency, horizontal stability, and vertical stability were assessed. Key-press behaviors responding to target jump were analyzed to evaluate functional eye movements. RESULTS: Compared with natural vision, horizontal eye position with respect to target position was less stable in simulated prosthetic vision at macular, superior, and nasal implant locations, in ascending order of the degree of instability. Vertical eye position with respect to target position in simulated prosthetic vision with the superior implant location was less stable in tracking slow target motion than fast. Eye movement latency in simulated prosthetic vision was longer than in natural vision. Key-press performance was impaired in simulated prosthetic vision. CONCLUSIONS: Pursuit eye movements in prosthetic vision, compared to natural vision, are significantly slower in initiation and less smooth in motion. They seem, however, still functional, even if the prosthesis is implanted in the peripheral retina. A superior implant locus may help the prosthesis wearer better control horizontal eye movements, which are more frequently used in the activities of daily living.