Morphological, functional and gene expression analysis of the hyperoxic XXXX retina.

@entity9327 @entity871 @entity19 @entity26 @entity16
This study examined the impact of prolonged (up to 35 day) exposure to @entity871 on the morphology and function of the retina, in the C57BL/6J @entity19 , as a basis for interpretation of gene expression changes. @entity19 of the C57BL/6J strain were raised from birth in dim cyclic illumination (12  h 5  lux, 12  h dark). Adult animals (90-110 days) were exposed to continuous @entity871 (75% @entity26 ) for up to 35  d. Retinas were examined after 0  d (controls), 3  d, 7  d, 14  d and 35  d. Spatial and temporal patterns of photoreceptor death were mapped, using the TUNEL technique. Immunohistochemistry and a specific assay were used to assess the expression of a stress-related protein ( @entity9327 ) and the activity of key antioxidant enzymes (SOD). The dark-adapted flash electroretinogram was used to assess the function of rods and cones. RNA hybridized to Affymetrix Genechips was used to assess gene expression during the first 3  d of exposure. Photoreceptors were stable during the first 7  d exposure to @entity871 , but thereafter showed progressive @entity16 , which began in a 'hot-spot' 0.5  mm inferior to the optic disc, then spread into surrounding retina. SOD activity was upregulated at 14  d, but not at earlier time points. @entity9327 expression was upregulated in M  ller cells from 3  d. Rod and cone components of the ERG were supernormal at 3  d and 7  d, but then fell below control levels. Gene expression changes suggested possible mechanisms for this early supernormality of function. At 14  d exposure, damage to and death of photoreceptors were prominent and spreading, and function was correspondingly degraded. However at 3  d exposure, @entity871 -induced supernormal functional responses in rods, while leaving their structure apparently undamaged. Variations in early (3 days) gene expression provide a partial insight into the mechanisms involved in this.
