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L Z Bito

Publications and source records attributed to L Z Bito.

At least 37 records · Page 2Linked to original sources
PubMed1989

Functional morphology of accommodation in the raccoon.

The raccoon (Procyon lotor) is a small carnivore which eats in the upright position, using hand- and finger-like front paws and digits to wash, hold and examine its food at close range. These anatomic and behavioral characteristics prompted structural and functional studies of the accommodative capability of this species. By light and electron microscopy, we observed a prominent ciliary smooth muscle and zonular apparatus. When stimulated by carbachol or pilocarpine, the muscle and zonular apparatus exhibited a shift from longitudinal to reticular or circular orientation of some ciliary muscle bundles, anterior movement of the muscle as a whole, and more oblique crossing of the zonular fiber bundles in the zonular plexus. Maximum carbachol-induced accommodative amplitude measured by coincidence refractometry ranged from 3 to 19 diopters in these 1 to 9 yr old animals, with no definite age-accommodation relationship. A-scan ultrasonographic biometry showed that during accommodation the lens thickened very little, if at all, but moved anteriorly, while the apparent cornea to retina distance increased slightly. The raccoon thus exhibits the greatest accommodative capability of any non-primate terrestrial mammal so far studied.

Accommodation, Ocular↗
PubMed1989

Maintained reduction of intraocular pressure by prostaglandin F2 alpha-1-isopropyl ester applied in multiple doses in ocular hypertensive and glaucoma patients.

In a randomized, double-masked, placebo-controlled study, 0.25 microgram (n = 11) or 0.5 microgram (n = 13) of prostaglandin F2 alpha-1-isopropyl ester (PGF2 alpha-IE) was applied topically twice daily for 8 days to one eye of ocular hypertensive or chronic open-angle glaucoma patients. Compared with contralateral, vehicle-treated eyes, PGF2 alpha-IE significantly (P less than 0.05) reduced intraocular pressure (IOP), beginning 4 hours after the first 0.5-microgram dose and lasting at least 12 hours after the fourteenth dose, with a significant (P less than 0.005) mean reduction of 4 to 6 mmHg maintained throughout the last day of therapy with either dose. A contralateral effect was not observed. Mean tonographic outflow facility was significantly (P less than 0.05) higher in PG-treated compared with vehicle-treated eyes (0.17 +/- 0.02 versus 0.12 +/- 0.01 microliter/minute/mmHg, respectively; +/- standard error of the mean) for the 0.5 microgram dose. Conjunctival hyperemia reached a maximum at 30 to 60 minutes after PGF2 alpha-IE application. Some patients reported mild irritation lasting several minutes after some doses. Visual acuity, accommodative amplitude, pupillary diameter, aqueous humor flare, anterior chamber cellular response, Schirmer's test, pulse rate, and blood pressure were not significantly altered. Our findings show that PGF2 alpha-IE is a potent ocular hypotensive agent and a promising drug for glaucoma therapy.

Aged↗
PubMed1989

The putative and demonstrated miotic effects of prostaglandins in mammals.

The foregoing clearly indicates that there are tremendous differences in the responsiveness of the iris sphincters of different mammalian species to the miotic effects of PGs. The iris sphincter of cats and dogs contracts in response to PGF2 alpha, but not in response to other PGs, at concentrations that can be expected to occur under in vivo physiological conditions. In both of these species, PGF2 alpha, but none of the other PGs tested, yielded a dose-dependent full miosis when applied topically to intact eyes. Although in vivo studies are not available on bovine eyes, in vitro studies show that the isolated bovine iris sphincter exhibits a contractile response in the presence of several PGs, but that the threshold concentration for this response is about hundred-fold higher than the concentration of PGF2 alpha required to cause a similar or an even larger effect on feline or canine iris sphincters. Thus, in contrast to the feline iris, the bovine iris shows low sensitivity and low specificity, exhibiting responses to high concentrations of several PGs. In vivo and in vitro studies also are in full agreement that the iris sphincter of several other species, including rabbits and diurnal primates (rhesus and cynomolgus monkeys, baboons, and humans) do not exhibit similar miotic responses to any of the PGs that had been studied so far. It is difficult to summarize all these findings in a truly quantitative manner because the in vitro studies have used different experimental conditions, especially with respect to the inhibitors or precontracting agents used, while in vivo studies have differed with respect to the form of the PG used and in the mode of its administration. These differences, together with the lack in some instances of adequate descriptions of experimental conditions, must be borne in mind in any effort to compare the effects of PGs on the iris sphincter of different species. Nevertheless, because of the importance of obtaining at least a semi-quantitative picture of the extent of these species differences, the data derived from reports on in vivo studies of miosis have been tabulated in the chapter dealing with the effects of PGs on IOP (see Bito et al., 1989). Results extracted from some of the in vitro studies that have been reviewed in the previous sections are summarized in Table 1. The readers are urged to study the original publications and to bear in mind the problems described in the preceding sections that are encountered when trying to interpret the results presented by van Alphen et al. (1977).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

The ocular effects of eicosanoids and other autacoids: historic background and the need for a broader perspective.

Great progress has been made in describing the synthesis of most known eicosanoids by ocular tissues. This progress has included identification of the spectrum of eicosanoids synthesized by different ocular tissues of different species, as well as comparisons of the relative proportion of individual eicosanoids produced by ocular tissues of different species. In contrast to this wealth of information, the lack of antagonists that are specific to individual eicosanoids has greatly hindered efforts to determine the specific ocular functions of each member of this family of autacoids. Furthermore, the absence of high-affinity ligands that are specific for individual eicosanoid receptors has greatly limited our ability to classify these receptors and to assign specific eicosanoid effects to specific cell types. In the early years of ocular PG research, the lack of recognition of the existence of parallel pathways of arachidonic acid metabolism and the lack of appreciation of the effects of some other autacoids--most notably the recently discovered neuropeptides--led to the premature conclusion that PGs have mediatory roles in a number of ocular pathophysiological responses. More recent studies have demonstrated that some ocular effects, such as chemotaxis, that were first attributed to classical PGs of the E and F type are actually mediated by eicosanoids synthesized by the lipoxygenase pathway, whereas other ocular responses, at least in some species, are mediated by various neuropeptides. These neuropeptides can be released by the same stimuli that cause the release of arachidonic acid. Furthermore, interpretation of the ocular effects of eicosanoids as well as neuropeptides has been complicated by large species differences in the effects of these autacoids on intraocular tissues. Among mammalian species, the rabbit eye and the primate eye may represent opposite extremes with respect to the extent of their responses to irritation and trauma, as well as with respect to their responses to some autacoids, especially eicosanoids and neuropeptides. In spite of these differences, the rabbit remains the animal most widely used in eye research. Consequently, many of the findings reviewed in this volume are also based on studies done only on rabbits. However, in view of the foregoing, we must resist the temptation to extrapolate to primates results obtained only from studies of rabbit eyes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

A physiological approach to glaucoma management: the use of local hormones and the pharmacokinetics of prostaglandin esters.

It appears that a pragmatic approach, based entirely on the ability of a drug or procedure to reduce IOP, has thus far been used to develop modalities for the management of glaucoma. Barring serendipity, it is unlikely that this approach will produce effective new methods for the management of this ocular disorder, which presents an ever-increasing problem in an increasingly longevous and industrialized world population. Although a better understanding of the biology of aqueous humor dynamics and its pathogenesis, combined with new genetic engineering techniques, may eventually lead to the total elimination of glaucoma, that ultimate solution is unlikely to be achieved within the foreseeable future. Thus, a physiologic approach to glaucoma management must be developed, one that takes into consideration all of our recently acquired knowledge of aqueous humor dynamics and all other relevant physiologic principles. A review of currently available information suggests that from a physiologic point of view the best approach to glaucoma management, at least for the next few decades, will be based on the use of receptor-mediated, naturally occurring ocular hypotensive agents, or at least agents that closely resemble such naturally occurring autacoids. Based on the temporal and spatial limitations of the various classes of receptor-mediated autacoids and on differences in the specificity and the nature of the responses they elicit at different sites, we conclude that a physiologic approach to glaucoma management should focus on the use of topically applied local hormones or their analogs. This approach appears to be feasible in light of demonstrations that several members of one family of local hormones, the eicosanoids that are produced within ocular tissues under physiological conditions are effective ocular hypotensive agents. It has been shown that one member of this family, PGF2 alpha, in its esterified form, is an extremely potent ocular hypotensive agent in its esterified prodrug form in both normotensive and glaucomatous human eyes, yielding significant IOP reduction when topically applied in doses less than one-hundredth that of currently available glaucoma medications. Although no intraocular side effects have been noted in human eyes after topical application of PGF2 alpha-1-isopropylester in submaximal ocular hypotensive doses, such side effects as conjunctival hyperemia and foreign body sensation present a problem and a challenge.4

Administration, Topical↗
PubMed1988

Presbyopia.

Explore the source record for details and available documents.

Aging↗
PubMed1987

The ocular pharmacokinetics of eicosanoids and their derivatives. 1. Comparison of ocular eicosanoid penetration and distribution following the topical application of PGF2 alpha, PGF2 alpha-1-methyl ester, and PGF2 alpha-1-isopropyl ester.

These experiments were undertaken to determine whether the increased ocular hypotensive potency of topically applied prostaglandin (PG) PGF2 alpha esters, as compared with that of PGF2 alpha free acid, can be accounted for by increased penetration of the eicosanoid moiety of the esterified PG into the eye. One hour after the topical application of [3H]PGF2 alpha-1-methyl ester (ME) in peanut oil, the 3H activities in the cornea, aqueous humor, and ciliary body of the rabbit eye were 32-, 22-, and 8-fold higher, respectively, than they were following the topical application of [3H]PGF2 alpha free acid. 3H activity during the first 3 hr declined rapidly in the cornea and more slowly in the aqueous humor, but remained essentially constant in the ciliary body for up to 6 hr, declining rapidly only between 6- and 24 hr. 3H activity in eyes that received [3H]PGF2 alpha ME was also several-fold higher in the anterior sclera and iris than in eyes that were treated with [3H]PGF2 alpha free acid, but this difference was much smaller in the conjunctiva. At 1 hr, most of the 3H activity in the aqueous humor was associated with PGF2 alpha, as determined by chromatography, but at 2- and 3 hr other peaks, presumably reflecting metabolites of PGF2 alpha, became apparent. The penetration and intraocular distribution of 3H activity was similar when [3H]PGF2 alpha ME was applied to the eye in normal saline rather than in peanut oil or when the isopropyl rather than the methyl ester of PGF2 alpha was used. These studies indicate that esterification of the carboxyl group of PGF2 alpha greatly enhances the penetration of the PGF2 alpha moiety into the eye and suggests that effective de-esterification of the PGF2 alpha ester occurs in the cornea, resulting in the delivery of PGF2 alpha free acid into the aqueous humor. It is concluded that topically applied PG esters act as pro-drugs and that the increased ocular penetration of these esters may account for the previously reported increase in their ocular hypotensive potency as compared to that of PG free acid or salts.

Administration, Topical↗
PubMed1987

Slit-lamp studies of the rhesus monkey eye. I. Survey of the anterior segment.

Slit-lamp photographic studies of 144 caged rhesus monkeys, aged 2 months to 35 years, show age-related changes in anterior-chamber depth, lens thickness, anterior and posterior curvatures of the lens, and location of the posterior lens surface relative to the anterior corneal surface. For these parameters, as well as for those measured by other techniques, a difference in slope magnitude and (or) slope sign was found between the growth phase which lasts for 5-6 years, and the adult phase (greater than 5-6 years). Age-related changes in the adult rhesus eye are qualitatively similar in almost all aspects to those observed in the human eye, indicating that the rhesus is a good animal model for the study of human loss of accommodative amplitude.

Aging↗
PubMed1987

Eicosanoids as a new class of ocular hypotensive agents. 1. The apparent therapeutic advantages of derived prostaglandins of the A and B type as compared with primary prostaglandins of the E, F and D type.

The classic primary prostaglandins (PGs), as well as some of their analogs and derivatives, are potent ocular hypotensive agents. The present studies show that A and B PGs, which are derived from PGs of the E type by dehydration and isomerization, have a much greater ocular hypotensive potency than the primary PGs of the E, F or D type. A single application of 5 micrograms of PGA2 to the cat eye in a 25-microliters volume of aqueous vehicle solution yielded a greater and more prolonged ocular hypotensive effect than as much as 100 micrograms of topically applied PGF2 alpha. As little as 1 microgram of PGA2 had a significant ocular hypotensive effect that was enhanced by three or more consecutive daily applications of the same dose. This IOP reduction, which remained significant for several days after the last of 10 daily treatments, was not associated with biomicroscopically detectable flare or invasion of the anterior chamber by cells. Although PGF2 alpha and, to a much lesser extent, PGE2 have a miotic effect in cats, PGs of the A and B type did not cause significant miosis even at doses 50- to 100-fold greater than the minimum dose required to yield significant ocular hypotension. PGA2 retained its ocular hypotensive potency when stored in an aqueous solution at room temperature for four months. The conjunctival hyperemia caused by 5 micrograms or 10 micrograms of A or B type PGs on rabbit eyes was milder and shorter in duration than that caused by the same doses of PGE2 or PGF2 alpha. These findings suggest that derived PGs, especially PGs of the A type, may have a therapeutic advantage over primary PGs for the treatment of ocular hypertension and glaucoma.

Administration, Topical↗
PubMed1987

Ocular development and aging. 1. Corneal endothelial changes in cats and in free-ranging and caged rhesus monkeys.

The endothelium of the cornea is said to retain its cellular proliferative capacity in rabbits but not in cats or primates. The present study was undertaken to determine whether the decline in cell density with increasing age is shared by all species that presumably lose their corneal endothelial-cell proliferative capacity and to determine whether in primates age-dependent changes in the endothelium are influenced by such environmental factors as light intensity and temperature. We found that in cats a very rapid decline in endothelial cell density during the first 10 months post partum was followed by a slower decline between 10 and 12 months, corresponding to a rapid increase followed by a slower rate of increase in corneal surface area. Between 1- and 14 years of age, a further decline in endothelial-cell density did not occur, and no endothelial pleomorphism or corneal guttata was observed among the 44 cats studied in this age group. In rhesus monkeys, an approximate 20% decline in cell density between 1 and 6 years of age, representing a period of ocular growth, was followed by a continuing decline in endothelial cell density at a slower rate of 0.7 to 0.8% per year throughout the rest of the lifespan, despite the fact that there was no evidence for further increase in globe size during this period of adulthood and aging. This rate of decline is similar to that described in the human corneal endothelium and was found to be the same in free-ranging animals continually exposed to high levels of solar radiation and in animals caged under artificial room light of much lower intensity and a year-round temperature of 21 +/- 1 degrees C. However, the animals maintained indoors showed a much higher frequency of endothelial pleomorphism than the free-ranging animals. These differences in age-dependent changes between feline and primate corneal endothelium and between primates living under grossly different environmental conditions are discussed.

Aging↗
PubMed1987

Presbyopia: an animal model and experimental approaches for the study of the mechanism of accommodation and ocular ageing.

During the last hundred years, observations on normal and a few aniridic human eyes, together with population studies on the age-dependent decline in accommodative amplitude, resulted in the formulation of theories of human accommodation, and led to the concept that presbyopia is an inevitable consequence of ageing. However, such studies failed to substantiate these theories and concepts or to reveal the fundamental mechanisms of accommodation and its age-dependent loss. Detailed understanding of these mechanisms and the environmental, dietary, and behavioural factors that may influence the development of presbyopia will require controlled studies and, in some cases, invasive experimental manipulations that can only be achieved through the use of an animal model. This paper reviews some of the evidence indicating that the rhesus monkey is a highly suitable primary animal model for such studies, as well as for studies on other aspects of ocular ageing, and reviews some of the techniques and experimental approaches that have already been adapted or developed for such studies.

Accommodation, Ocular↗
PubMed1987

Ocular trace metal kinetics and toxicology. I. The distribution of intravitreally injected 67Cu++ within intraocular compartments and its loss from the globe.

Radioactive copper (67Cu++) was injected into the center of the vitreous body of rabbits. The relatively rapid initial loss of 67Cu from the vitreous was associated with its accumulation in intraocular tissues. At 24 hr, 20% of the injected 67Cu was found in the retina, representing the highest 67Cu concentration among all ocular tissues, and this high 67Cu concentration was maintained in this tissue throughout the 10-day observation period. Significant amounts of 67Cu were not detected in the aqueous humor at any time. About one-half of the injected 67Cu was lost from the whole globe in 5 days, but the remaining Cu was retained in the globe during the next 5 days. Eyes that received a large dose of CuSO4 in addition to the tracer showed decreased 67Cu activity in the retina and a slight increase in the aqueous humor. Endotoxin-induced ocular inflammation decreased the rate of 67Cu loss from the vitreous, reduced its accumulation by the retina, and increased 67Cu entry into the aqueous humor. It is concluded that 67Cu is retained in the vitreous and the globe due to its binding by, and/or uptake into, intraocular tissues, especially the retina. Cu does not effectively enter the anterior chamber from the vitreous, apparently due to its effective removal by the ciliary processes, thus ruling out the possibility of identifying the existence of Cu-containing intraocular foreign bodies in the posterior segment of the eye by analysis of Cu in the aqueous humor.

Animals↗
PubMed1987

Eicosanoids as a new class of ocular hypotensive agents. 2. Comparison of the apparent mechanism of the ocular hypotensive effects of A and F type prostaglandins.

It has recently been shown that derived prostaglandins (PGs) of the A and B types are much more potent ocular hypotensive agents than primary PGs of the E, F, or D type. The purpose of this study was to determine whether two representatives of these structurally different PGs, namely PGA2 and PGF2 alpha-1-isopropyl ester (PGF2 alpha IE), reduce intraocular pressure (IOP) of the feline eye by similar or dissimilar mechanisms. Aqueous humor flow rate was determined by a fluorophotometric technique, Schiotz electronic tonography was used to measure outflow facility and venomanometry was done to measure episcleral venous pressure. Although at the doses used, both PGF2 alpha IE (2.5 micrograms/eye) and PGA2 (5.0 micrograms/eye) caused significant IOP reduction within 2.5 hr after their topical application, neither caused a significant decrease in aqueous humor flow rate, a significant increase in outflow facility or a change in episcleral venous pressure. It was concluded, therefore, that both of these PGs reduce IOP by an apparently similar mechanism, presumably by increasing uveoscleral outflow.

Animals↗
PubMed1986

The pathophysiology of the ocular microenvironment. II. Copper-induced ocular inflammation and hypotony.

The ocular effects of intravitreally injected copper sulfate solutions were studied in New Zealand white rabbits. These injections resulted in uveitis characterized by prolonged ocular hypotony, increased protein concentrations and decreased ascorbic acid concentrations in both the vitreous and aqueous humors, and an apparent decrease in the transport function of the anterior uvea. The extent and the duration of these effects were dose-dependent. The lower doses used, 3 or 6 micrograms of Cu as CuSO4 per eye, produced reversible inflammation. The highest dose, 30 micrograms of Cu per eye, also produced some signs of ocular chalcosis: hemorrhage, vitreous liquefaction, prolonged hypotony and local iridial ischemia. Six hours after the intravitreal injection of 6 micrograms of Cu as CuSO4 per eye, the Cu concentration in the vitreous humor increased to approximately 100 times that in the vitreous of control eyes, and began to decline only 3 days later, with a half-time of approximately 8 days. The Cu concentration in the anterior chamber of these eyes never exceeded 1 ppm and returned close to control values within 3 days. Based on these findings, factors that affect ocular trace-metal distribution and kinetics are discussed, as are reasons for the apparent difficulty in diagnosing the presence of Cu-containing intraocular foreign bodies on the basis of the Cu concentration of the aqueous humor.

Animals↗
PubMed1986

Transport of prostaglandins and other eicosanoids by the choroid plexus: its characterization and physiological significance.

Choroid plexi from the lateral ventricles of rabbits, cats, and dogfish (Mustelus canis) were used to characterize the prostaglandin (PG) uptake process and to establish its kinetic parameters and substrate specificity. The apparent Kt for PGF2 alpha transport by the rabbit choroid plexus was 20 microM; the Jmax was 27 nmol g-1 min-1. The Ki of inhibition of PGF2 alpha transport by PGE2 was 20 microM; the Jmax of PGF2 alpha transport was unaltered by PGE2. A concentration of p-aminohippuric acid of up to 1 mM did not appreciably affect the Kt or the Jmax of PGF2 alpha transport. The rate of PGF2 alpha accumulation by rabbit choroid plexus was reduced by incubation at 4 degrees C, under anaerobic conditions, in the absence of sodium or in the presence of ouabain, probenecid, or bromcresol green. The choroid plexi of all three species also accumulated thromboxane B2, PGI2, and 6-keto-PGF1 alpha, suggesting that most, if not all, eicosanoids are substrates for this transport system. It is concluded that the choroid plexus transport system satisfies all the criteria of an active, energy-dependent transport system and that this system functions effectively at concentrations of eicosanoids present in the ventricular system under normal or pathological conditions. Hence, this transport system must make an important contribution to the pharmacokinetics of eicosanoids within the brain.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Prostaglandins and other eicosanoids: their ocular transport, pharmacokinetics, and therapeutic effects.

Since prostaglandins (PGs) were originally discovered in the eye in a search for the mediators of the ocular irritative responses, it is not surprising that the first decade of research on the ocular effects of these autacoids concentrated on their potential role in inflammation and other pathological processes. It is clear that PGs, like most other biologically active compounds, can have pathological effects when introduced into the eye in sufficiently high doses. More recent studies indicate, however, that PGs are also involved in the normal physiological processes of the eye, and that some PGs effectively reduce intraocular pressure and may actually moderate rather than mediate ocular inflammation. We must therefore consider the eicosanoids as a new class of potential ocular therapeutic agents. This paper reviews the evidence that these autacoids are actively transported by some tissues, including the ciliary epithelium, and considers the role of such transport processes in the ocular and systemic pharmacokinetics of endogenous eicosanoids and their therapeutically applied prodrugs.

Animals↗