Variation of binocular-vertical fusion amplitude with convergence.

PURPOSE: The maximum binocular vertical disparity that can be fused with disparity vergence (vertical-fusion amplitude or VFA), varies with convergence angle. VFA is larger for convergence responses to near than to far viewing distances; however, the clinical norms for changes in VFA with convergence have not been established. VFA at several convergence angles was measured to obtain a quantitative description of the changes in VFA with convergence. METHODS: Fifty-six adults took part in the study. Horizontal and vertical disparity stimuli were presented on a computer monitor by using the red-green anaglyphic technique. Stimulus to convergence was altered either by changing horizontal disparity on the computer monitor (experiment I: nine horizontal disparities: 1.2-22.5 PD [Delta]) or by changing the binocular viewing distance (experiment II: five viewing distances: 25-300 cm). Convergence was held constant during an experimental session, while vertical disparity was incremented in steps of 0.05 Delta after a subjective report of fusion, until the subject reported diplopia. The maximum vertical disparity that could be fused was defined as the VFA. RESULTS: VFA increased linearly over the range of convergence stimuli (y = 0.10x + 1.62) and intersubject variability of VFA increased marginally with the amount of convergence. Linear regression equations with similar slopes and y-intercepts were observed in experiments I and II. CONCLUSIONS: The results of the experiments provide a quantitative description of a linear relationship between VFA and convergence. The linear regression equation could be used in a clinical setting to establish norms and to screen for vertical vergence abnormalities.

Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha.

Hypoxia profoundly influences tumor development and response to therapy. While progress has been made in identifying individual gene products whose synthesis is altered under hypoxia, little is known about the mechanism by which hypoxia induces a global downregulation of protein synthesis. A critical step in the regulation of protein synthesis in response to stress is the phosphorylation of translation initiation factor eIF2alpha on Ser51, which leads to inhibition of new protein synthesis. Here we report that exposure of human diploid fibroblasts and transformed cells to hypoxia led to phosphorylation of eIF2alpha, a modification that was readily reversed upon reoxygenation. Expression of a transdominant, nonphosphorylatable mutant allele of eIF2alpha attenuated the repression of protein synthesis under hypoxia. The endoplasmic reticulum (ER)-resident eIF2alpha kinase PERK was hyperphosphorylated upon hypoxic stress, and overexpression of wild-type PERK increased the levels of hypoxia-induced phosphorylation of eIF2alpha. Cells stably expressing a dominant-negative PERK allele and mouse embryonic fibroblasts with a homozygous deletion of PERK exhibited attenuated phosphorylation of eIF2alpha and reduced inhibition of protein synthesis in response to hypoxia. PERK(-/-) mouse embryo fibroblasts failed to phosphorylate eIF2alpha and exhibited lower survival after prolonged exposure to hypoxia than did wild-type fibroblasts. These results indicate that adaptation of cells to hypoxic stress requires activation of PERK and phosphorylation of eIF2alpha and suggest that the mechanism of hypoxia-induced translational attenuation may be linked to ER stress and the unfolded-protein response.