Gene expression profiling of the retina after transcorneal electrical stimulation in wild-type Brown Norway rats.

PURPOSE: Transcorneal electrical stimulation (TES) has been beneficial in several neurodegenerative ocular diseases, but the exact mechanisms remain to be elucidated. This study was conducted to investigate the effects of TES on the retinas of wild-type Brown Norway (BN) rats by gene expression profiling and to assess its effects on retinal function and morphology. METHODS: TES was applied to BN wild-type rat retinas in vivo for 1 hour (1-ms biphasic pulses at 20 Hz; 200 µA). RNA was isolated and processed for microarray-based profiling 4 hours after TES; differentially expressed genes from TES compared with those from sham-treated animals were validated by quantitative real-time polymerase chain reaction. Furthermore, the effect of TES was assessed at the structural and functional levels using electroretinography, confocal scanning laser ophthalmoscopy, optical coherence tomography, and immunohistochemistry. RESULTS: Transcriptome changes associated with TES versus sham-stimulated BN wild-type retina were identified. Four hundred ninety genes were differentially expressed in TES and included potentially neuroprotective genes such as Bax or members of the tumor necrosis factor family (Tnfrsf11b, Tnrsf12a, Tnfsf13b, Tnfsf13). ERG recordings showed physiological retinal function after TES, and structural in vivo and ex vivo studies revealed intact retinal anatomy. CONCLUSIONS: These results demonstrate that TES applied to the retina of the wild-type BN rats induces distinct transcriptome level changes and may help in the understanding of the mechanisms underlying TES. In addition, TES treatment indicates no negative effect on structure and function of the wild-type BN retina up to 35 hours after application.

Effects on colour discrimination during long term exposure to high altitudes on Mt Everest.

AIM: To investigate changes in colour discrimination as a result of chronic hypoxic exposure induced by extreme altitudes (above 8000 m) during an expedition to Mt Everest. METHODS: Colour discrimination thresholds for tritan, protan and deutan axes were measured extensively in two male participants (four eyes) during an expedition to Mt Everest, using a quantitative, computer controlled psychophysical colour vision test (modified version of the Cambridge Colour Test). The tests were carried out over a period of 54 days at altitudes of 1300 m, 3450 m, 4410 m, 5060 m, 5300 m, 6450 m, 7200 m and 8000 m. RESULTS: Colour vision tests 1 week before and 6 months after the expedition indicated normal colour discrimination in both participants. With increasing altitude, colour discrimination thresholds were found to rise, predominantly for the tritan (blue) axes in both observers. Deutan (green) thresholds were minimally elevated at high altitude, whereas protan (red) was altered in one observer. Tritan colour discrimination thresholds decreased as a function of time spent at a given altitude and normalised upon return to low altitude. CONCLUSIONS: Chronic hypoxia induced by high altitude exposure transiently affects colour discrimination, in particular tritan axis discrimination. Decreased tritan discrimination is partly reversible upon physiological adaptation to high altitude and completely normalised upon return to low altitude.