Purpose: Accommodation responds to wavefront vergence, but the mechanisms for vergence detection are unknown. One possibility is that accommodation responds to the angle of incidence of light at edges blurred by defocus. ‘Averse channels’ that sample light from opposite sides of the pupil were hypothesized by Makous (1968, 1977). Makous named the phenomenon a “transient” Stiles-Crawford effect because he found that there was a reduction in sensitivity to light entering one side of the pupil that lasts for a short period of time. Such ‘averse channels’ that sample modulation across the pupil are a possible mechanism for detecting the sign of defocus. The purpose of the present experiment is to determine whether such ‘averse channels’ can operate separately of each other to specify the sign of defocus for accommodation. Method: Accommodation was monitored continuously while subjects viewed a vertical monochromatic (548nm) luminance edge (1.0 contrast) that stepped either to a far or near direction in a Badal optometer. Various levels of adapting field were used to reduce the contrast of the edge (0.48, 0.36, 0.26, or 0.17 contrast) to determine the contrast threshold for accommodation. In a final experiment, an adapting field entered the eye through the nasal or temporal side of the pupil, to selectively adapt nasally or temporally tuned ‘channels’, while the target stepped randomly toward or away from the eye. The orientation of the vertical edge was either bright on the right side or bright on the left. Results: In a preliminary experiment, only five out of twenty-six subjects showed reliable and consistent responses, with gains >0.5 for both positive and negative step change in vergence. The contrast threshold for accommodation to step changes in target vergence was approximately 26%. Data from three subjects who accommodated reliably to both directions of step changes in vergence do not support the claim that ‘channels’ sample light separately from opposite sides of the pupil to determine the sign of defocus. Conclusion: Potential factors that account for the poor accommodative responses in the present study include: 1) the target was illuminated with monochromatic light, 2) the target was a simplified stimulus in which the blur was in only one direction (one spatial phase), 3) the target was viewed monocularly, 4) the 3mm artificial pupil increased depth-of-focus and removed the normal dynamic behavior of the pupil, 5) our subjects were untrained. The negative results suggest alternate hypotheses: 1)‘averse channels’ work in conjunction with each other, not separately, to detect vergence, 2) ‘averse channels’ can function separately to detect vergence, but the signal was undetectable using the current method, and 3) ‘averse channels’ do not mediate vergence detection.

Epidermal growth factor, EGF, is one of the essential growth factors that stimulates injury-induced corneal epithelial healing rates. Cell signaling contributors mediating this response include capacitative calcium entry (CCE) activation and protein kinase C (PKC) isoform stimulation. This study shows in human corneal epithelial cells, HCEC, that CCE is preferentially activated by the PKC isoforms  and . Moreover such activation requires increases in plasma membrane Ca2+ influx through store-operated channels. Therefore, EGF-induced stimulation of cell proliferation and migration may depend on unique effects mediated by six different PKC isoforms identified in HCEC. TRPV1 is a vanilloid subtype of the transient receptor potential protein superfamily. This isoform is a subunit of a non-selective cation channel mediating downstream responses to heat, low pH, or noxious stimuli. TRPV1 expression has been recently described in some epithelial tissues and induces proinflammatory cytokine release through mitogen-activated protein kinase (MAPK) superfamily stimulation. This study describes in HCEC the signaling pathways mediating TRPV1-induced increases in proinflammatory cytokine release. It suggests that epithelial TRPV1 receptor activation by noxious stimuli contributes in-vivo to mounting proinflammatory reactions.

PURPOSE: To design a contrast sensitivity perimetry test with the potential to improve clinical management of glaucoma by decreasing test-retest variability in defective areas while maintaining good sensitivity to glaucomatous loss. METHODS: Twenty patients with glaucoma, ten age-similar control subjects and ten young control subjects were recruited. One eye was tested per subject. All subjects were tested with contrast sensitivity perimetry (CSP), and conventional automated perimetry (CAP). Stimuli for CSP were Gabor patches with a peak spatial frequency of 0.375 cpd and a two-dimensional spatial Gaussian envelope with the most of the energy concentrated within a central circular region 4 degrees in diameter. For CSP, stimuli were presented at 26 locations over the central visual field, excluding the central 5 degrees and with the emphasis on the nasal hemifield. Neuroretinal rim area of the patients was measured using retinal tomography (HRT II). Young subjects were tested on CSP using 4-reversal and 8-reversal staircases to estimate variability and test duration. Bland-Altman analysis of agreement was used to assess test-retest variability, to compare depth of defect for the two perimetric tests, and to investigate the relation between contrast sensitivity and neuroretinal rim area. RESULTS: With 4-reversal staircases, for both Size III stimuli and Gabor stimuli, variability increased as sensitivity decreased (r2 > 5%, p<0.001), but at a shallower rate for the Gabor stimuli (Z > 2.9, p<0.005). With 6- and 8- reversal staircases, the correlation between sensitivity and variability was not significant (r2 = 0.05%, p>0.5) and the slope of the regression line was shallower than for the 4-reversal staircases (Z>2.4, p< 0.01). Depth of defect was on average similar for the two devices, but for some patients the size III stimuli tended to yield deeper defects than Gabors in regions of lower sensitivity. The relation between rim area and perimetric sensitivity was more consistent for contrast sensitivity perimetry than for conventional perimetry (Z=9.3, p < 0.0005). For control subjects there was a significantly shallower decline in sensitivity with eccentricity using Gabor stimuli than with conventional size III stimuli (Z=3.78, p<0.0005), and overall test-retest variability was similar for staircases with 4 to 8 reversals. CONCLUSION: Contrast sensitivity perimetry demonstrated reasonably low test-retest variability and good ability to detect defect. It also showed a structure-function relation that was independent of the degree of glaucomatous loss. Further research on contrast sensitivity perimetry is needed to evaluate its utility in monitoring progression of glaucoma and effects of treatment.