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Biomedical subjects

M L Sears

Publications and source records attributed to M L Sears.

At least 37 records · Page 2Linked to original sources
PubMed1985

Regulation of aqueous flow by the adenylate cyclase receptor complex in the ciliary epithelium.

The answer to how the beta-adrenergic receptor mediates a fall in intraocular pressure has been elusive. Methods of measurement have not been refined sufficiently. The separate changes after adrenergic treatment frequently are small, and the tissue effects are multiple. On a molecular basis, stimulation of the beta-adrenergic receptor activates intracellular adenylate cyclase to produce increased cyclic adenosine monophosphate. Acting by different cell-receptor mechanisms, but nonetheless potent, nonadrenergic stimulators of adenylate cyclase in the ciliary epithelium, such as cholera toxin and organic fluorides, have been studied in experimental animals. They reduce intraocular pressure by reducing net aqueous flow. When forskolin, a diterpene and potent stimulator of adenylate cyclase, became available, it was used in noninvasive topical form in the human eye to clarify the question of whether increased cyclic adenosine monophosphate reduces intraocular pressure and aqueous flow. Noninvasive studies in human eyes have demonstrated a 35% reduction in outflow pressure after the administration of forskolin in a 1% topical suspension, matched by a corresponding reduction in aqueous flow. Tonographic outflow facility was unaltered. Thus, the entire reduction in intraocular pressure can be accounted for by a reduction in net aqueous flow.

ADP-Ribosylation Factors↗
PubMed1985

Effects of somatostatin, a somatostatin analog, neurotensin and met-enkephalin in the eye with special reference to the irritative response.

The effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 micrograms/eye) and infused intra-arterially (0.6-4 micrograms/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 micrograms neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 micrograms met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met-enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory nerves.

Animals↗
PubMed1985

Cervical ganglionectomy alters the circadian rhythm of intraocular pressure in New Zealand White rabbits.

A circadian rhythm of intraocular pressure in rabbits could provide a useful model for understanding the daily rhythm of intraocular pressure in humans and for studying mechanisms which regulate intraocular pressure. Our results confirm earlier work showing that New Zealand White rabbits housed in an environment with a lighting cycle of 12 hours light and 12 hours dark have a rhythm of intraocular pressure, and that this rhythm persists in constant dark. We show further that the cycle of light and dark is the zeitgeber for entrainment of the rhythm of intraocular pressure, and therefore persistence of this rhythm in constant dark establishes it as a circadian rhythm. Cervical ganglionectomy demonstrated that intact sympathetic innervation to the eye is required for maintenance of the normal circadian rhythm of intraocular pressure in rabbits. Intraocular pressure in sympathectomized eyes is no different from control eyes during the light, but is significantly reduced during the dark.

Animals↗
PubMed1984

Ocular effect of neodymium-YAG laser.

We aimed a high-powered pulsed neodymium-YAG laser incrementally from air to the anterior portion of the vitreous in rabbits to evaluate its effect on the corneal endothelium, the lens, and the dynamics of intraocular fluid. Corneal endothelium damage occurred as much as 3.5 mm away from the site of optical breakdown. The degree of tissue damage was inversely proportional to the distance from the site of optical breakdown, and the damage pattern at a given distance was the same whether the optical breakdown was anterior or posterior to the corneal endothelium. A single 4-mJ shot (mode-locked train) of laser light causes disintegration and liquefaction of the lens in a spherical area 300 micron in diameter. The damage extends posteriorly to a distance of 450 micron. The effect of this explosion denatures the surrounding cortical fibers for an area of 50 to 80 micron. Increased intraocular pressure was noted in all instances of anterior or posterior capsulotomy, probably as a result of the release of liquefied cortical material and mechanical obstruction of the chamber angle. No increase in intraocular pressure occurred when the lens capsule remained intact.

Animals↗
PubMed1984

Aqueous flow in human eyes is reduced by forskolin, a potent adenylate cyclase activator.

Forskolin, which lowers intraocular pressure in rabbits, monkeys, and human subjects, was tested for its effect on the rate of aqueous humor flow and on outflow facility. Topical sodium fluorescein was used to measure the rate of aqueous humor flow in forskolin or placebo treated eyes. Tonography was used to determine outflow facility before forskolin administration and at 3 hr after administration of the drug. In eight human subjects who showed reduction of intraocular pressure in response to a single drop of forskolin, flow was reduced by an average of 34%, compared to the contralateral eye during the same period of time. No significant change in outflow facility occurred. The action of forskolin in reducing intraocular pressure was the direct result of a reduction in net aqueous flow.

Adenylyl Cyclases↗
PubMed1984

Aphakic cystoid macular edema. The pharmacology of ocular trauma.

Ocular tissues, like those of other organs, exhibit limited morphologic reactions to trauma, i.e., hyperemia, abrupt vasodilation, increased blood flow; increased permeability of blood vessels, edema and increased tissue pressure (disrupted blood-ocular barrier); and later, a cellular inflammatory response. The cystoid macular edema (CME) that occurs after surgery for cataract has a considerably higher incidence in more severely traumatized eyes. It is characterized by increased perifoveal capillary permeability that may be related either to prior vasoconstriction or to vasodilation, and it may be accompanied by a cellular inflammatory response either in the (uvea) ciliary body, vitreous, or retina, or in combination thereof. Virtually all the physiologic, metabolic, and morphologic responses to trauma can be assigned to liberation of endogenous mediators. The lesions that occur after ocular trauma may be related to the synthesis and release of prostaglandins. There is moderate support for this hypothesis, but other or additional endogenous mediators must also be considered as contributing to the production of retinal edema as a nociceptive response to trauma. The various factors that may contribute to development of CME, and their mechanisms of action, are discussed. The speculations and hypotheses contained in this review need to be confirmed or denied by applications to the eye of techniques that have been used successfully in other organ systems. Adequate prophylaxis may be provided by cyclooxygenase inhibitors, but it is more likely accomplished with corticosteroids. However, definitive clinical tests have not been done, and it should be noted that excellent surgery with minimal disruption of the blood-ocular barrier is the best prophylaxis for this iatrogenic disease. When the lesion is established and does not respond to large doses of corticosteroids, a careful study is needed to decide whether vitreous inflammation and/or strand formation accounts for the irreversibility.

Animals↗
PubMed1984

The histopathology of black ball hyphema: a report of two cases.

Two black ball clots manually expressed through limbal incisions four and seven days after total traumatic hyphema were examined histologically. The surface of both clots consists of a fibrin "pseudocapsule" with no attachments to intraocular structures. There is a cohesive internal structure formed by concentric fibrin layers. No fibroblastic or neovascular activity was present. Intracameral clots evolve differently than intravascular clots. True organization of the black ball hyphema clot does not appear to take place within the first seven days after black ball hyphema secondary to contusion trauma.

Adolescent↗
PubMed1980

Beta-adrenergic receptors in ciliary processes of the rabbit.

Identification and characterization of beta-adrenergic receptors were attempted in particulate membrane fractions derived from isolated ciliary processes (CP) of rabbit eyes. High-affinity binding sites for 125I-hydroxybenzylpindolol (125I-HYP), a beta-adrenergic antagonist, were identified in particulate membrane fractions of homogenized CP that were recovered from discontinuous sucrose density gradients. Adenylate cyclase activity was recovered in the same fraction as the 125I-HYP binding sites. The dissociation constant of 125I-HYP for the high affinity site is 0.25 nM, with a minimum capacity of about 35 fmol/mg of protein. Adrenergic agonists and antagonists, including timolol, 1-alprenolol, d,1-propranolol, 1-isoproterenol, 1-epinephrine, and phentolamine, were examined for their ability to displace 125I-HYP from its binding site. The results were consistent with the identification of the high-affinity 125I-HYP binding sites as beta-adrenergic receptors. This is the first report which identifies by ligand binding techniques beta-adrenergic receptors in CP exclusive of iridial or other uveal tissue and supports the possibility of direct action of beta-adrenergic agents on the formation of aqueous humor.

Adenylyl Cyclases↗
PubMed1978

The presence of lysosomal hyaluronidase in the rabbit iris.

Lysosomal hyaluronidase in the rabbit iris was studied by means of a sensitive assay method based on carbocyanine dye binding. The enzyme activity in the lysosomal extract was proportional to both the enzyme concentration and the incubation time. When the enzyme was heated, the enzyme activity was lost completely. When the lysosomal extract was used as an enzyme source, the enzyme activity was protected by pepstatin. The enzyme had a pH optimum of 3.8 and no activity above pH 5.0.

Animals↗
PubMed1978

Distribution of acid phosphatase, beta-glucuronidase, and lysosomal hyaluronidase in the anterior segment of the rabbit eye.

Distribution of acid phosphatase, beta-glucuronidase, and lysosomal hyaluronidase in the anterior segment of the rabbit eye was studied biochemically. Acid phosphatase activity was higher in the anterior uvea and cornea but lower in the sclera. Beta-Glucuronidase activity was higher in the anterior uvea but lower in the corneoscleral tissues. Lysosomal hyaluronidase activity was higher in the anterior uvea. The inner layer of the corneoscleral junction showed the highest specific activity of beta-glucuronidase and lysosomal hyaluronidase among the corneoscleral tissues. Lysosomal hyaluronidase activity was detected in all corneoscleral tissues.

Absorption↗
PubMed1977

Leber's congenital amaurosis.

An early stage of Leber's congenital amaurosis, characterized by white spots or lines in the fundus, occurred in two children. Light microscopic examination of eyes obtained from one child, a 16-month-old Japanese girl, revealed subretinal deposits corresponding to the white spots and lines in the fundus deposits. Light and electron microscopic examination of the eye showed distinctive changes in the outer retinal layers and choroid, while the inner retinal layers were nearly normal. Characteristic early lesions of congenital amaurosis appeared to be produced by deposits consisting of loose outer segments and apical processes of the pigmental epithelial cell and macrophages. Undifferentiation in the nuclei of the photoreceptor cell, the inner segment, the pigment epithelial cell, and the choriocapillaris were likely characteristics of the early changes of congenital amaurosis.

Blindness↗
PubMed1977

Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit.

The effect of timolol, propranolol, epinephrine, and isoproterenol on intraocular pressure (IOP) (measured by tonometry) were compared after topical administration in conscious rabbits. Epinephrine and isoproterenol decreased IOP in normotensive rabbits, whereas propranolol had no effect. Timolol produced only a slight and inconsistent lowering of IOP in normotensive rabbits. All four agents reduced IOP elevated by an oral water load; the adrenergic agonists were substantially more active than the two beta-adrenergic blocking agents. In alpha-chymotrypsin-induced ocular hypertension, epinephrine, isoproterenol, and timolol were essentially equally effective, whereas propranolol exhibited only weak activity. In this latter model, timolol did not lose its effectiveness after multiple instillations (three/day) over an 8-day period. The concentration of timolol in the acqueous humor after topical application of effective hypotensive doses was relatively high as compared to that found in plasma. In addition, topical doses of timolol required to lower IOP were considerably greater than those needed to reduce or block the ocular hypotensive activity of isoproterenol. The mode of action and therapeutic implications of beta-adrenergic blocking agents in glaucoma are discussed.

Adrenergic beta-Antagonists↗
PubMed1976

Differential reactivity of rabbit iris and ciliary process to topically applied prostaglandin E2 (dinoprostone).

The topical application of prostaglandin E2 (dinoprostone) is followed by massive swelling of the ciliary process, leading to substantial leakage of marker dye into the posterior chamber and directly into the region of the iris, where the primary ciliary processes insert. In contrast, blood vessels of the iris proper retain most of their normal barrier quality and do not leak Evans blue dye. The adrenergic innervation of the anterior segment remains normal in density and in quality after the topical application of PGE.

Administration, Topical↗