Latrunculin-A causes mydriasis and cycloplegia in the cynomolgus monkey.
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PURPOSE: To determine the effect of latrunculin (LAT)-A, which binds to G-actin and disassembles actin filaments, on the pupil, accommodation, and isolated ciliary muscle (CM) contraction in monkeys. METHODS: Pupil diameter (vernier calipers) and refraction (coincidence refractometry) were measured every 15 minutes from 0.75 to 3.5 hours after topical LAT-A 42 microg (approximately 10 microM in the anterior chamber [AC]). Refraction was measured every 5 minutes from 0.5 to 1.5 hours after intracameral injection of 10 microl of 50 microM LAT-A (approximately 5 microM in AC), with intramuscular infusion of 1.5 mg/kg pilocarpine HCl (PILO) during the first 15 minutes of measurements. Pupil diameter was measured at 1 and 2 hours, and refraction was measured every 5 minutes from 1 to 2 hours, after intravitreal injection of 20 microl of 1.25 mM LAT-A (approximately 10 microM in vitreous), with intramuscular infusion of 1.5 mg/kg PILO during the first 15 minutes of measurements (all after topical 2.5% phenylephrine), and contractile response of isolated CM strips, obtained <1 hour postmortem and mounted in a perfusion apparatus, to 10 microM PILO +/- LAT-A was measured at various concentrations. RESULTS: Topical LAT-A of 42 microg dilated the pupil without affecting refraction. Intracameral LAT-A of 5 microM inhibited miotic and accommodative responses to intramuscular PILO. Intravitreal LAT-A of 10 microM had no effect on accommodative or miotic responses to intramuscular PILO. LAT-A dose-dependently relaxed the PILO-contracted CM by up to 50% at 3 microM in both the longitudinal and circular vectors. CONCLUSIONS: In monkeys, LAT-A causes mydriasis and cycloplegia, perhaps related to its known ability to disrupt the actin microfilament network and consequently to affect cell contractility and adhesion. Effects of LAT-A on the iris and CM may have significant physiological and clinical implications. (+info)
Relative potency of levo-alpha-acetylmethadol and methadone in humans under acute dosing conditions.
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levo-alpha-Acetylmethadol (LAAM) and methadone are full mu-opioid agonists used to treat opioid dependence. Current labeling indicates that LAAM is less potent than methadone. Clinical studies have not determined the relative potency of these drugs. This study compared the effects of acute doses of LAAM and methadone and also examined the ability of naloxone to reverse their effects. Five occasional opioid users received once weekly doses of either placebo, LAAM, or methadone (15, 30, or 60 mg/70 kg p.o.) in agonist exposure sessions and then received naloxone (1.0 mg/70 kg i.m.) 24, 72, and 144 h after agonist exposure. Subject-rated, observer-rated, and physiological measures were assessed regularly. Comparisons of physiological and subjective measures collected in agonist exposure sessions indicate that LAAM is not less potent than methadone under acute dosing conditions. For some measures, LAAM was significantly more potent. Three subjects who entered the study were withdrawn for safety reasons due to greater than anticipated and clinically relevant respiratory depression after receiving 60 mg of LAAM. Naloxone did not fully reverse the pupil constriction produced by 60 mg of LAAM. Acute agonist effects suggest that LAAM may be more potent than methadone and more potent than current labeling indicates. An accurate LAAM:methadone relative potency estimate will aid determination of adequate doses for opioid-dependent patients inducted onto LAAM and for methadone maintenance patients who choose to switch to more convenient thrice-weekly LAAM. (+info)
Cone spacing and waveguide properties from cone directionality measurements.
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Reflectometric techniques estimate the directionality of the retinal cones by measuring the distribution of light at the pupil plane of light reflected off the bleached retina. The waveguide-scattering model of Marcos et al. [J. Opt. Soc. Am. A 15, 2012 (1998)] predicts that the shape of this intensity distribution is determined by both the waveguide properties of the cone photoreceptors and the topography of the cone mosaic (cone spacing). We have performed two types of cone directionality measurement. In the first type, cone directionality estimates are obtained by measuring the spatial distribution of light returning from the retina with a single-entry pupil position (single-entry measurements). In the second type, estimates are obtained by measuring the total amount of light guided back through the pupil as a function of entry pupil position (multiple-entry measurements). As predicted by the model, single-entry measurements provide narrower distributions than the multiple-entry measurements, since the former are affected by both waveguides and scattering and the latter are affected primarily by waveguides. Measurements at different retinal eccentricities and at two different wavelengths are consistent with the model. We show that the broader multiple-entry measurements are not accounted for by cone disarray. Results of multiple-entry measurements are closer to results from measurements of the psychophysical Stiles-Crawford effect (although still narrower), and the variation with retinal eccentricity and wavelength is similar. By combining single- and multiple-entry measurements, we can estimate cone spacing. The estimates at 0- and 2-deg retinal eccentricities are in good agreement with published anatomical data. (+info)
Human dynamic closed-loop accommodation augmented by sympathetic inhibition.
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PURPOSE: A ciliary alpha-adrenoceptor accommodative effect has been proposed, caused by a small population of alpha1-inhibitory receptors in excised human ciliary muscle. This study was intended to investigate the effect on the closed-loop dynamic accommodative process of modulating alpha1-adrenoceptor activity by topical instillation of the alpha1-adrenergic agonist, phenylephrine hydrochloride. METHODS: A group of 10 visually normal subjects viewed a photopic (30 candela/m2) high-contrast Maltese cross, which was modulated sinusoidally (0.05-0.6Hz) and stepwise over a 2-D range (2-4 D). Monocular temporal accommodation responses were measured using a continuously recording dynamic tracking infrared optometer under two trial conditions: after instillation of saline control solution and 50 minutes subsequent to the instillation of 0.27 microl 0.4% benoxinate hydrochloride and 0.27 microl 2.5% phenylephrine hydrochloride. Pupil size and accommodative amplitude were measured at 90-second intervals for 50 minutes after drug instillation. All accommodative measurements were recorded through a fixed 4-mm pupil. RESULTS: A significant reduction in accommodative amplitude (11%; P < 0.05) was recorded, whereas pupil size showed a significant increase (33%; P < 0.05). No significant change in step-response dynamics was observed. However, phenylephrine hydrochloride caused a significant increase in accommodative gain in the low and midtemporal frequency ranges compared with the effect of a saline control treatment. No significant variation in phase lag was observed. CONCLUSIONS: For the first time in humans, this study shows that augmentation of the alpha1-inhibitory sympathetic contribution results in increased accommodative gain at low and midtemporal frequencies, which is consistent with findings in animal studies. (+info)
The depth-of-field of the human eye from objective and subjective measurements.
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The depth-of-field (DOF) measured through psychophysical methods seems to depend on the target's characteristics. We use objective and subjective methods to determine the DOF of the eye for different pupil diameters and wavelengths in three subjects. Variation of image quality with focus is evaluated with a double-pass technique. Objective DOF is defined as the dioptric range for which the image quality does not change appreciably, based on optical criteria. Subjective DOF is based on the accuracy of focusing a point source. Additional DOFs are obtained by simulation from experimental wavefront aberration data from the same subjects. Objective and subjective measurements of DOF are only slightly affected by pupil size, wavelength and spectral composition. Comparison of DOF from double-pass and wavefront aberration data allows us to evaluate the role of ocular aberrations and Stiles-Crawford effect. (+info)
S-cone contribution to pupillary responses evoked by chromatic flash offset.
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On a green or red background, the action spectrum of the pupillary responses evoked following the offset of chromatic test flashes shows a prominent short-wavelength lobe and suggests the contribution from photoreceptors other than the previously inferred M- and L-cones (Kimura & Young, Vision Research (1996). 36, 1543-1550), most likely from S-cones. Systematic changes in the shape of the intensity versus amplitude functions with test wavelengths and in the shape of the short-wavelength lobe with response amplitude criteria suggest an antagonistic interaction involving the short- and longer-wavelength photoreceptors. (+info)
Changes in corneal wavefront aberrations with aging.
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PURPOSE: To investigate whether corneal wavefront aberrations vary with aging. METHODS: One hundred two eyes of 102 normal subjects were evaluated with videokeratography. The data were decomposed using Taylor and Zernike polynomials to calculate the monochromatic aberrations of the cornea for both small (3-mm) and large (7-mm) pupils. RESULTS: For a 3-mm pupil, the amount of total aberrations (Spearman rank correlation coefficient r(s) = 0.145; P = 0.103) and spherical-like aberrations (r(s) = -0.068; P = 0.448) did not change with aging, whereas comalike aberrations exhibited a weak but statistically significant correlation with age (r(s) = 0.256; P = 0.004). For a 7-mm pupil, total aberrations (r(s) = 0.552; P < 0.001) and comalike aberrations (r(s) = 0.561; P < 0.001) significantly increased with aging, but spherical-like aberrations showed no age-related changes (r(s) = 0.124; P = 0.166). Simulated pupillary dilation from 3 mm to 7 mm caused a 38.0+/-28.5-fold increase in the total aberrations, and the extent of increases significantly correlated with age (r(s) = 0.354; P < 0.001). Pupillary dilation influenced the comalike aberrations more in the older subjects than in the younger subjects (r(s) = 0.243; P = 0.006), but such age dependence was not found for spherical-like aberrations (r(s) = 0.141; P = 0.115). CONCLUSIONS: Comalike aberrations of the cornea correlate with age, implying that the corneas become less symmetrical along with aging. Spherical-like aberrations do not vary significantly with aging. Pupillary dilation markedly increases wavefront aberrations, and those effects are more prominent in older subjects than in younger subjects. (+info)
Pupillographic findings in neglect.
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OBJECTIVES: Unilateral sensory neglect has been attributed to various defects, including a hemispatial attention-arousal deficit. However, support for this hypothesis has only been indirect. Therefore, the purpose of this study was to further test the hemispatial attentional-arousal hypothesis by measuring pupillary response as an index of arousal. METHODS: There were two experimental subjects with neglect and six matched controls. Stimuli (Arabic numbers) were presented on the right, left, and centre of a screen. The subjects were asked to look at the number in the centre, on the right, or left of the screen while their pupil diameter was measured. RESULTS: Unlike the control subjects, the subjects with neglect, who were aware of the left sided stimuli, did not show a pupillary dilatation when they looked at the stimulus on the left. CONCLUSIONS: Although this study provides support for the hemispatial attention-arousal hypotheses of neglect, it does not preclude the possibility that other mechanisms may also be important. (+info)