Biomedical subjects
M L Sears
Publications and source records attributed to M L Sears.
Immunocytochemical localization of Na/K-ATPase in the isolated ciliary epithelial bilayer of the rabbit.
This study examined the localization of Na/K-ATPase in a specially isolated ciliary epithelial bilayer of the rabbit. This bilayer, harvested by a technique developed in this laboratory, consisted of pigmented epithelial (PE) and non-pigmented epithelial (NPE) cells free of stroma and with a well preserved ultrastructural morphology. Immunocytochemical localization of Na/K-ATPase was performed using goat anti-rabbit Na/K-ATPase with the biotin-streptavidin peroxidase method on fresh as well as fixed preparations. The most prominent immunostaining was found along the basolateral infoldings and interdigitations of both NPE and PE cells. This finding suggests that both ciliary epithelial layers participate in active ion transport and the production of aqueous humor.
Visual field loss in glaucoma.
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Friedenwald lecture: Perspectives in glaucoma research.
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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.
The use of sympathetic nervous system agents in the treatment of glaucoma.
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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.
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.
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.
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.
Objective evaluation of experimental ocular irritation.
After topically administered nitrogen mustard the irritative effect on the pupil, intraocular pressure, protein concentration of the aqueous humor and on the vessels of the iris and conjunctiva was quantified. The protein level in aqueous was determined by refractometry. The degree of hyperemia of conjunctiva and iris was determined by measuring the amount of Evans blue dye present in the tissue minutes after intravenous administration. A reproducible relationship was obtained using these methods to evaluate the degree of irritation produced by nitrogen mustard.
The effect of dopamine on the intraocular pressure and pupil of the rabbit eye.
The presence of a dopamine-specific receptor that can influence intraocular pressure in the rabbit eye is suggested by these experiments: intravitreal, systemic, or topically administered dopamine solutions can produce a decrease in intraocular pressure that is dose-dependent. In high doses the decrease in intraocular pressure is accompanied by mydriasis, and alpha-adrenergic pupillary response. This alpha-response may be caused by dopamine as a direct, but weak alpha-stimulator or by displacement of norepinephrine onto the receptor from its storage site. At lower doses the decrease in intraocular pressure occurs in the absence of mydriasis and in spite of blockade of beta-adrenergic receptors. Further, a specific dopaminergic blocker, haloperidol, prevents this decrease in intraocular pressure. The decreases are small, but reproducible and suggest that dopamine can influence the adrenergic regulation of intraocular pressure.
The effect of d-isoproterenol on intraocular pressure of the rabbit, monkey, and man.
D-isoproterenol d-bitartrate applied topically lowers intraocular pressure (IOP) in normal albino rabbits and rabbits with alpha-chymotrypsin-induced glaucoma. This effect is independent of any effect on systemic blood pressure or pulse rate. A similar response could not be obtained in monkey or human eyes. Subconjunctival injection of d-isoproterenol d-bitartrate to monkey eyes did not alter IOP.
The contralateral effect of antidromic stimulation of the trigeminal nerve on the rabbit eye.
The effect on contralateral eyes after injuries to one eye has been called the consensual reaction and has been postulated to be either the consequence of a neural reflex or one achieved by circulating substances. Trigeminal stimulation always causes ipsilateral miosis, ocular hyperemia, intraocular hypertension, and a disruption of the blood-aqueous barrier. Disruption of the blood-aqueous barrier in the contralateral eye after stimulation of the trigeminal nerve always occurs and depends on intact sensory innervation to that globe in rabbits. The disruption is not prevneted by pretreatment of the animals with indomethacin. The phenomenon of disruption of the barrier is sometimes accompanied by an elevation of intraocular pressure in the contralateral eye but not by the other irritative responses. Thus, unilateral stimulation of a sensory nerve, the trigeminal, in the rabbit, can produce ipsilateral contralateral disruption of the blood-aqueous barrier.
Potentiation of the effects of topical epinephrine on the pupil and intraocular pressure in the sympathetically denervated rabbit eye by a catechol-O-methyl transferase inhibitor.
Dose-response curves of increase in pupil size and decrease in intraocular pressure with topical epinephrine have been determined in the sympathetically denervated rabbit eye. Topical pretreatment with the catechol-O-methyl transferase inhibitor U-0521 potentiated the effects of epinephrine on both the pupil and pressure. These observations suggest a possible role for catechol-O-methyl transferase in the aqueous humor dynamics of the supersensitive eye. The possible use of the denervated rabbit eye as an experimental model for the glaucomatous eye in evaluating the ocular effects of adrenergic agents is discussed.
[Disruption of the blood-aqueous barrier demonstrated by histofluorescence microscopy (author's transl)].
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Morphology of the breakdown of the blood-aqueous barrier in the ciliary processes of the rabbit eye after prostaglandin E2.
Protaglandin E2, administered topically to the rabbit eye, causes disruption of the blood-aqueous barrier resulting in a large increase in the protein content of the aqueous humor. The route of plasma proteins into the aqueous humor was studied with the electron microscope, using horseradish peroxidase as a protein tracer. The tracer penetrated the tight junctions of the nonpigmented layer of the ciliary epithelium, filling the lateral intercellular clefts and staining the internal limiting membrane. These morphological studies confirm the prior physiologic demonstration that, in response to prostaglandin, plasma proteins enter the posterior chamber via the intercellular clefts of the nonpigmented epithelium.