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Biomedical subjects

J K Lauber

Publications and source records attributed to J K Lauber.

At least 19 recordsLinked to original sources

Three avian eye enlargement protocols as myopia models: effects of pharmacological intervention.

Myopia is a prevalent condition threatening vision in half or more of the individuals in some subpopulations and at some ages. The etiology is unknown. It is not even clear whether myopia has several possible causes or only one, whether the condition is inherited or acquired. Suggested counter measures have ranged from behavior modification during the growing years through various medications, to surgical intervention. It is suggested that answers to these questions must lie in research exploring how the eye develops, how it serves its owner. A common finding in most cases of myopia is that the eyeball is too long axially, thus the image from a distant object comes to sharp focus in front of, rather than at, the retina. Accommodation increases the refractive power of the eye and is counterproductive in a myope. Nonetheless, one suggested treatment has been to suppress accommodation by paralyzing the ciliary muscles. Another theory suggests that high intraocular pressure causes eye enlargement, thus the anti-glaucoma drugs have sometimes been recommended. We report here some trials involving drugs given to chicks with light-induced avian glaucoma, a syndrome characterized by moderate to severe myopia, and elevated intraocular pressure.

Animals↗

Review: avian models for experimental myopia.

Myopia poses a serious threat to unaided vision among the human population, affecting as much as fifty per cent or more of individuals in some subpopulations and at some age levels. Because the etiology of the condition remains obscure, attention has been directed toward a search for experimental animal models for myopia: the hope is that any environmental or experimental intervention found to increase eye size, especially axial length, or to lead to negative refractive error, may suggest some parallels in clinical experience. As well, the availability of myopic animal subjects affords the opportunity to test the efficacy of both preventative and pharmacological measures as they become available.

Animals↗

Kainic acid and formoguanamine effects on environmentally-induced eye lesions in chicks.

Several neurotoxins are known which destroy some specific retinal component or other link in the visual pathway. We have employed such reagents to induce blindness in chicks, in order to explore the role of vision in the development of light-induced avian glaucoma (LIAG) and/or lid-suture myopia (LSM). Chicks made pharmacologically blind with formoguanamine failed to develop LSM. Under LIAG conditions, increased eye weight and global enlargement did not occur, but the characteristic anterior segment changes were seen. Thus LIAG globe enlargement, and LSM axial lengthening, appear to be vision-driven, but anterior segment changes are probably separately controlled. The retinal neurotoxin kainic acid rendered chicks behaviorally blind in the eye into which it was injected intravitrially, but this failed to prevent LIAG changes in either anterior segment or growth of the globe. Chicks reared under LSM conditions, and treated with kainic acid were not different from untreated controls, in that they developed globe enlargement in spite of their pharmacologically-induced blindness. Preliminary trials with quisqualic acid, another retinal neurotoxin, indicate that this agent, like kainic acid, cannot prevent LIAG eye enlargement. Several quis-treated eyes developed phthisis bulbi however, and thus could not be included among those assessed for eye weight and dimensional measurements.

Animals↗

Melatonin reduction by lithium and albinism in quail and hamsters.

Melatonin was measured by radioimmunoassay in several genetic strains of Japanese quail. Plasma melatonin (PM), measured at the nighttime peak, was highest in wild type quail reared on a diurnal lighting schedule; this PM peak was suppressed in continuous light. Albino quail had low melatonin levels, whether reared under diurnal conditions or in continuous light. Ocular melatonin was also suppressed in albinos and in dilute mutants. At midday sampling, melatonin was only half as high in albinos as in wild types. Intraocular pressure (IOP, daytime readings) was uniformly low in diurnal birds and was elevated in all quail reared under continuous light. Thus in pigmented birds, a high melatonin level was associated with high IOP, but in albinos displaying high IOP, ocular melatonin was not elevated. Lithium chloride, mixed in the feed, brought about a pronounced reduction in plasma, pineal, and ocular melatonin, in wild-type quail reared on a diurnal schedule. This confirms earlier findings in lithium-fed rats. Golden hamsters displayed a characteristic diurnal cycle of pineal melatonin, with a sharp middark peak; in albino hamsters, also kept on a diurnal schedule, this peak occurred at the same time, but albinos had melatonin levels only about one-third as high as those of pigmented animals.

Albinism↗

Ocular responses of genetically blind chicks to the light environment and to lid suture.

Blind rc chicks were examined as to growth characteristics of the developing eye. We also explored the relationship between hereditary blindness and two environmental interventions affecting eye development, light-induced avian glaucoma (LIAG) and the axial lengthening associated with lid-suture. Genetically blind rc chicks could be identified by their behavior even during the first hours after hatching. However, they retained the pupillary reflex, at least to 5 weeks of age. Blind chicks reared under a diurnal lighting schedule had eyes 18% larger (by eye weight) than sighted hatchmates, with corresponding increases in globe diameters. Of the anterior segment parameters, neither corneal diameter, anterior chamber depth nor corneal curvature was demonstrably different from sighted controls. When rc chicks were reared under continuous light, the environmental condition which brings on LIAG, their already enlarged eyes showed no superimposed increases in either eye weight or globe dimensions. The corneas showed some characteristic LIAG effects: small anterior chamber depth and increased corneal radius of curvature (flat cornea), as compared with diurnal rc birds. Some birds were subjected to unilateral eyelid-suture, a protocol which usually induces axial lengthening and corneal bulging. Blind rc birds did not respond to this surgical intervention: in comparison by paired t-test between sutured and contralateral eye, there was little or no difference in eye weight, globe diameters or anterior segment parameters. Thus vision, or at least an intact retina/RPE, seems to be necessary for development of the characteristic axial lengthening in response to eyelid suture. The globe enlargement of LIAG also appears to be vision-dependent, although the anterior segment manifestations of LIAG are systemic effects.

Animals↗

Adjustment of sleep and the circadian temperature rhythm after flights across nine time zones.

The adjustment of sleep-wake patterns and the circadian temperature rhythm was monitored in nine Royal Norwegian Air-force volunteers operating P-3 aircraft during a westward training deployment across nine time zones. Subjects recorded all sleep and nap times, rated nightly sleep quality, and completed personality inventories. Rectal temperature, heart rate, and wrist activity were continuously monitored. Adjustment was slower after the return eastward flight than after the outbound westward flight. The eastward flight produced slower readjustment of sleep timing to local time and greater interindividual variability in the patterns of adjustment of sleep and temperature. One subject apparently exhibited resynchronization by partition, with the temperature rhythm undergoing the reciprocal 15-h delay. In contrast, average heart rates during sleep were significantly elevated only after westward flight. Interindividual differences in adjustment of the temperature rhythm were correlated with some of the personality measures. Larger phase delays in the overall temperature waveform (as measured on the 5th day after westward flight) were exhibited by extraverts, and less consistently by evening types.

Aerospace Medicine↗

Chicks blinded with formoguanamine do not develop lid suture myopia.

The involvement of the retina in avian lid suture myopia was investigated by use of formoguanamine (FG), which induces blindness in chicks, characterized by damage to the retinal pigment epithelium and photoreceptor layers. In control chicks reared under a diurnal lighting schedule of 12L/12D, unilateral eyelid suture at 3 days of age induced a typical lid suture myopia response on the operated side (eye enlargement and bulging cornea) by 4 wks. of age. On the other hand, in FG-treated blind chicks also reared under 12L/12D, there was no difference in eye parameters, between sutured and non-sutured eyes. All globe parameters measured were very similar in FG-treated and control non-sutured chicks. Corneal diameter and anterior chamber depth in the eyes of FG-treated chicks were significantly smaller than in non-sutured control eyes.

Animals↗

Plasma corticosterone in chicks reared under several lighting schedules.

Plasma corticosterone was determined by radioimmunoassay in 6-7-week-old male broiler type chicks, reared under several carefully controlled lighting regimes. When subjects were grouped by photoperiod of rearing, chicks reared in darkness had significantly lower hormone levels than diurnal controls, or than subjects reared in continuous light. Around-the-clock sampling revealed a diurnal corticosterone rhythm, with high daytime levels and lower night-time levels. This rhythm appeared to be retained in constant light, although phase shifted or free running. Neither analysis by light intensity level nor by lights on/lights off status at the time of blood sampling revealed differences in plasma corticosterone between the experimental groups which could be attributed to these factors.

Animals↗

Light-induced avian glaucoma as an animal model for human primary glaucoma.

Glaucoma can be induced in domestic chicks at the will of the investigator, by the simple device of rearing the chicks under continuous light. This light-induced avian glaucoma (LIAG) is presented as an animal model system for human open-angle glaucoma. A number of morphological and physiological findings in LIAG are reviewed, and the LIAG system is compared with several other glaucoma model systems, in dogs, rabbits and monkeys. Intraocular pressure in LIAG has been demonstrated to be responsive to several anti-glaucoma drugs, and the system could be used for further drug testing. Thus it is suggested that LIAG may be especially useful in studies seeking to understand human glaucoma, and how to forestall it, or treat it. As well, a prolonged "pre-glaucoma" period is available to the investigator working with LIAG, during which a pathological course is already underway in the eye, but intraocular pressure has not yet gone up.

Animal Husbandry↗

Lid suture myopia in chicks.

Domestic chicks reared under continuous light developed light-induced avian glaucoma (LIAG), including eye enlargement and flat cornea. Chicks reared under dim light developed dim light buphthalmos (DLB), a somewhat similar eye enlargement, superimposed on the LIAG effect when, as in one subgroup of the present experiments, the dim light was also continuous. Unilateral lid suture elicited experimental myopia on the operated side, additive to the LIAG and/or DLB effects. When the rearing conditions were diurnal (ie, not such as to induce LIAG eye enlargement), and the light of at least "normal" brightness, lid suture still caused unilateral myopia, accompanied by a pronounced bulging of the cornea. We discuss the probable effects of these changes on refraction and accommodation during the chick's development.

Animals↗

Light, experimental avian myopia and the role of the suprarenals.

Domestic chicks reared under continuous dim light developed the eye enlargement and suppressed corneal growth characteristic of light-induced avian glaucoma (LIAG) and dim light buphthalmos (DLB). Administered corticosterone moderated these effects on both the globe of the eye and the cornea. The anti-adrenal agent Metyrapone had no discernable effects on the globe parameters of the eye, although the cornea was somewhat enlarged and the anterior chamber deeper than in controls. Mitotic rate in the corneal epithelium, and adrenal and testis weight, were more sensitive indicators, showing that both the hormone and its antagonist induced changes in these experimental subjects.

Adrenal Cortex↗

Plasma melatonin rhythm lost in preglaucomatous chicks.

Domestic chicks (Gallus domesticus) reared under continuous light, and thus developing light-induced avian glaucoma (LIAG), were tested at 4-hourly intervals around the clock, for evidence of hormonal or other rhythms which might be related to the eye effects of LIAG. Plasma melatonin, corticosterone and thyroxine (T4) all displayed daily rhythms in the young chick reared under control (diurnal) lighting conditions. These daily hormone cycles were somewhat damped under either continuous light or constant darkness, though there were hints of a surviving rhythm, albeit phase-shifted or free-running, in plasma corticosterone and T4. In the eye, mitotic rate in the corneal epithelium displayed a prominent rhythm, high in the dark and low in the light. This rhythm was suppressed by constant darkness, and also in continuous light, the latter apparently related to the impaired corneal growth of LIAG. The daily pattern of corneal mitotic activity and the diurnal curve for plasma melatonin showed remarkable similarities, suggesting the possibility of a causal relationship between the two phenomena.

Animals↗

International aircrew sleep and wakefulness after multiple time zone flights: a cooperative study.

An international research team has carried out an electroencephalographic study of sleep and wakefulness in flight crews operating long-haul routes across seven or eight time zones. Following baseline recordings, volunteer crews (n = 56) from four airlines spent their first outbound layover at a sleep laboratory. This paper provides an overview of the project's history, its research design, and the standardization of procedures. The overall results are remarkably consistent among the four participating laboratories and strongly support the feasibility of cooperative international sleep research in the operational arena.

Adult↗

N-acetyltransferase activity and melatonin level in the eyes of glaucomatous chickens.

The possible involvement of a melatonergic mechanism in the control of intraocular pressure (IOP) and the genesis of light-induced avian glaucoma (LIAG) was studied by measuring N-acetyltransferase (NAT) activity and melatonin levels in the iris, ciliary body and retina-choroid during the course of LIAG development, and in normal subjects by day and night. NAT activity was found to be significantly higher than normal in preglaucomatous and glaucomatous chicken eyes at 8, 16, and 24 weeks of age. The increase in NAT activity corresponded well with the decrease in aqueous outflow facility and preceded the development of elevated IOP by 5-6 weeks. Melatonin levels in iris and ciliary body of normal chickens and rabbits were elevated by night relative to day, which corresponded to the diurnal change in IOP. The melatonin levels in glaucomatous chicken iris and ciliary body at 24 weeks were significantly elevated relative to controls. The results suggest that melatonergic mechanisms could be involved in the elevation of IOP in LIAG. No statistical differences in choline acetyltransferase activity, adrenergic transmitter levels or dopamine concentrations could be found in tissues of LIAG eyes vs control eyes, indicating that cholinergic, adrenergic and dopaminergic mechanisms are probably not involved in LIAG.

Acetyltransferases↗

Timolol and pilocarpine are hypotensive in light-induced avian glaucoma.

Two antiglaucoma drugs were tested on Hubbard chicks with light-induced avian glaucoma (LIAG). This animal model for open-angle glaucoma was further assessed by a novel method for monitoring aqueous inflow and outflow simultaneously. When the chicks were 8 to 9 weeks of age the preglaucomatous eyes were significantly enlarged (p less than 0.001), weighing a mean of 3.37 g, compared with 2.59 g for a group of normal eyes, but the intraocular pressure (IOP) was slightly lower in the former (13.79 v. 16.46 mm Hg; p less than 0.05). At this age the aqueous outflow was markedly reduced (to 0.70 v. 2.47 microL/min; p less than 0.05), but no change in aqueous inflow could be demonstrated. By 18 to 20 weeks the glaucomatous eyes were further enlarged (mean weight 4.67 v. 3.76 g; p less than 0.001) and hypertensive (mean IOP 29.85 v. 22.27 mm Hg; p less than 0.05). Timolol elicited a 29% to 33% reduction in the IOP at 8 to 9 weeks in both groups of eyes. At 18 to 20 weeks it reduced the IOP of the glaucomatous eyes to normal values but caused a less marked reduction in the normal eyes. Pilocarpine elicited an initial sharp rise in the IOP but was ultimately hypotensive, causing about a 33% decrease from the preinfusion IOP, in both young and adult birds.

Animals↗

Sites and action spectra for encephalic photoreception in the Japanese quail.

Sexually mature Japanese quail, Coturnix coturnix japonica, were transferred to short environmental photoperiod for 20 days, during which they received encephalic illumination via surgically implanted optic fibers. White light delivered to discrete sites in the basal hypothalamus induced photogonadal response for testicular maintenance. There was also a strong positive response to monochromatic red, green, or blue light delivered to these areas, and this response was of equal magnitude regardless of wavelength. Illumination of sites in the median eminence and pars nervosa was also effective in inducing photogonadal response. White light delivered to the optic chiasma was effective, whereas green or blue light to this structure had no effect. Illumination of the preoptic hypothalamus or the dorsal cortex was also without effect. Our data indicate that there are photoreceptive sites in and near the basal hypothalamus that, when illuminated directly, are capable of responding to a broad range of visible wavelengths.

Animals↗