Albino spatial vision as an instance of arrested visual development.

Adult albinos and human infants share a number of common visual characteristics: both have low grating acuity, both lack a foveal pit (foveal hypoplasia), and both have much lower central cone densities than in the normal adult. We have explored the consequences of these characteristics by measuring both spatial and temporal contrast sensitivity in the central retina and by comparing central and peripheral grating and vernier acuities in two young adult albino subjects. To compensate for nystagmus, horizontally oriented patterns were employed. Both subjects had normal flicker sensitivities, but their central grating and vernier acuities were approximately five times worse than normal. At 10.0 degrees in the inferior visual field, however, vernier and grating acuities were normal for both subjects. Finally, the ratio of grating to vernier acuity in albino central vision fell within the normal foveal range, suggesting that albino central vision does not resemble the adult periphery. These results are consistent with the hypothesis that spatial processing deficiencies in albino central vision are a direct consequence of the increased spacing of their central cones. Our data are comparable to available psychophysical results obtained from infants of approx. 10 months of age, thus suggesting that the albino visual system may represent a case of arrested development.

Spatial frequency and orientation tuning of spatial visual mechanisms in human albinos.

A masking paradigm was used to measure the spatial frequency and orientation tuning of spatial mechanisms in the albino visual system. Threshold elevation curves obtained in this manner at test spatial frequencies of 0.25 cycles/deg (cpd), 0.50 cpd, and 1 cpd have the same shape as curves obtained from normal subjects at test frequencies two octaves higher. Additional masking studies showed that contrast processing in albinos obeys the same compressive power law as in normals. Thus, spatial mechanisms in albino central vision have normal spatial frequency and orientation bandwidths. As central cones in the albino are spaced 3-4 times further apart than in the normal fovea, these results support the hypothesis that monocular spatial vision in albinos is primarily limited by this increased receptor spacing. It is hypothesized that this, in turn, is the result of arrested development of the albino retina.

Effect of mycophenolate mofetil (RS-61443) on cytokine production: inhibition of superantigen-induced cytokines.

The effects of the immunosuppressant mycophenolate mofetil (MPAM, RS-61443) on cytokine production at the single cell level were assessed using in vitro activated human mononuclear cells. Cytokine production was studied with UV microscopy of fixed and permeabilized cells stained with cytokine specific monoclonal antibodies (mAbs). The cytokines evaluated included interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10 interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), TNF-beta, and granulocyte macrophage-colony stimulating factor (GM-CSF). MPAM exhibited a marked antiproliferative effect without cytotoxicity in all mononuclear cell cultures. Six to 24 hours after stimulation with the superantigen Staphylococcus aureus enterotoxin A (SEA), most cytokine production was unaffected by MPAM at therapeutic concentrations (10(-6) M), with the exception of GM-CSF. In contrast, by 48 h after antigen activation, MPAM significantly inhibited all studied cytokine production (p < 0.05). Cyclosporin A (CsA), used as a control at a concentration of 100 ng/ml, inhibited production of all studied cytokines, at all time points. Monokine production after lipopolysaccharide (LPS) stimulation was unaffected by MPAM. Similarly, the production of most of the cytokines studied after mitogen stimulation with phorbol ester (PMA) plus calcium ionophore (ionomycin) was not affected by MPAM, in comparison to CsA which demonstrated significant inhibition of all cytokines tested under these conditions. However, a late inhibitory effect on IL-3 production was seen by MPAM at 48 h after mitogenic stimulation. Further observations are required to explain the divergent results on cytokine production by MPAM in superantigen-activated and mitogen-activated human mononuclear cells.