Analysis of vitreous and aqueous levels of hyaluronic acid: application of high-performance liquid chromatography.
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Animals↗
Biomedical subjects
M C Koss
Publications and source records attributed to M C Koss.
Role of norepinephrine in the rabbit ganglionectomy response.
Superior cervical ganglionectomy (SCG) produced delayed mydriasis and ocular hypotension in rabbits. Norepinephrine (NE) was lost from the iris-ciliary body exponentially with onset of about 11 h. NE in aqueous humor peaked at twice control levels (from 7 to 14 ng/ml) at 16.5 h and subsequently declined to below control levels by 24 h. Intracameral administration of radiolabeled NE (150 ng) to control eyes resulted in a calculated outflow of 1.6 microliter/min, comparable to that seen with fluorescein (1.7 microliter/min). NE administered to ganglionectomized eyes (26 h after surgery) resulted in a calculated outflow of 3.1 microliter/min. These results suggest that mydriasis following SCG may be due to NE released from degenerating sympathetic nerve endings. However, NE concentration in the aqueous humor appears inadequate to produce the delayed increase in outflow observed in rabbits after SCG.
Animals↗
Laser-induced glaucoma in rabbits.
Argon laser energy was applied to the trabecular meshwork of pigmented rabbits in an attempt to develop an animal model of 'glaucoma'. Laser energy was varied to determine the optimal level needed to produce sustained ocular hypertension. An initial response of ocular hypertension followed by hypotension was observed in all of the animals tested. Approximately half of the laser-treated rabbits developed a secondary buphthalmus and sustained ocular hypertension. In these animals outflow facility was decreased by approximately 60%. Histologic examination at 4- and 8 weeks after laser treatment demonstrated a wound-healing response resulting in closure of the intertrabecular spaces and obstruction of outflow to injected carbon particles. Optic nerve cupping and a loss of ganglion cells were also observed. Topical application of L-timolol (0.5%), pilocarpine (2.0%) and forskolin (1.0%) were found to be effective in decreasing intraocular pressure in the laser-treated, hypertensive eye with no significant effect in control non-laser-treated eyes, suggesting that this model can be a useful tool for screening potential antiglaucoma medications.
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Pupillary dilation as an index of central nervous system alpha 2-adrenoceptor activation.
In recent years there has been increasing evidence that some antihypertensive drugs like clonidine and alpha-methyldopa (after conversion in the brain to alpha-methylnorepinephrine) may decrease sympathetic tone by stimulating central nervous system (CNS) alpha 2-adrenoceptors. These same drugs also produce pupillary dilation in cats and rats. In this review, evidence is presented supporting the hypothesis that clonidinelike drugs act either directly or indirectly on CNS postsynaptic alpha 2-adrenoceptors to cause pupillary dilation by reduction of parasympathetic neural tone to the iris. It is further suggested that the underlying physiologic mechanism for this mydriatic action is activation of an ascending pathway that provides tonic inhibitory input by releasing norepinephrine on neurons in the Edinger-Westphal complex. Yohimbine-sensitive pupillary dilation in these species may provide a simple and effective model for quantitatively accessing CNS alpha 2-adrenoceptor activity.
Adrenergic alpha-Agonists↗
Synaptic organization in the oculomotor nucleus.
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Animals↗
Histologic study of a neodymium-YAG laser sclerostomy.
A glaucoma filtering procedure was performed with the YAG laser in an eye to be enucleated for malignant melanoma. Scanning electron microscopic examination shows the extent and position of the incision and the effects of the procedure on the cornea. To our knowledge, this article represents the first report of complete perforation of the sclera in a living human eye with the use of a laser alone.
Cornea↗
Neodymium-YAG laser sclerostomy in primates.
A one-stage sclerostomy procedure was performed "noninvasively" in four cynomolgus monkeys solely with the neodymium-YAG laser. The neodymium (Nd)-YAG laser was focused, for the most part, a few diopters behind the focus of the helium-neon aiming beam. This enabled optical breakdown to occur entirely within the sclera to produce a perforating micropuncture of the scleral tissue. Two monkeys were treated with higher energy (23 and 24 joules) and two were treated at lower energy levels (12 and 14 joules). An immediate reduction of intraocular pressure in the treated eye was associated with a significant increase in outflow facility. The sclerostomy remained patent for more than 180 days, as determined by tonography and histologic examination. Scanning electron microscopic examination of the cornea revealed no significant damage to the central cornea or to tissue adjacent to the visual axis in any of the treated eyes. However, there was some endothelial cell loss at the site of the laser treatment at the peripheral cornea and in the area immediately posterior to the incision; there was also a focal break in Descemet's membrane.
Animals↗
Studies on the mechanism of clonidine-induced mydriasis in the rat.
Intravenous administration of clonidine hydrochloride (3-100 micrograms/kg) produced a dose-dependent pupillary dilation in anaesthetized rats. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level. Clonidine-induced mydriasis was present only in those preparations having intact parasympathetic neural tone to the iris. Depletion of CNS monoamines by more than 95% with reserpine (5 mg/kg) and alpha-methyl-para-tyrosine (2 X 300 mg/kg) failed to alter the dose-response relation to clonidine. Pretreatment with the alpha-2-adrenoceptor antagonist, yohimbine hydrochloride (1.5 mg/kg), produced about a 10-fold shift to the right in the pupillary dose-response curve to clonidine. Yohimbine administered after the highest dose of clonidine also antagonized the mydriatic response. The above results suggest that clonidine acts on CNS post-synaptic alpha-2-adrenoceptors to produce mydriasis by withdrawal of parasympathetic neural tone to the iris. In an attempt to assess the physiological substrate(s) involved, mydriatic responses, due to parasympatho-inhibition, were evoked by electrical stimulation of ascending (sciatic nerve and medullary) and descending (hypothalamic) pathways. Yohimbine (0.3 and 1.0 mg/kg) produced a dose-dependent inhibition of the pupillary dilation evoked by stimulation of the sciatic nerve and medullary loci, whereas these doses of yohimbine failed to alter the dilation in response to hypothalamic stimulation. Similarly, monoamine depletion greatly antagonized the pupillary dilation elicited by sciatic nerve and medullary stimulation without significantly affecting mydriasis due to hypothalamic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Ocular effects of adrenergic stereoisomers in the rabbit.
Because of the need to develop ocular hypotensive agents with low incidence of side effects, the dextrorotatory enantiomers of adrenergic agents have prompted some attention. In the present study, the relative potency and efficacy of various adrenergic stereoisomers with respect to their ocular hypotensive and mydriatic effects have been determined after topical administration to conscious rabbits. The relative order of potency was found to be, iris: 1-epinephrine much greater than d-epinephrine congruent to 1-norepinephrine congruent to dl-alpha-methyl-norepinephrine greater than dl-alpha-methyl-epinephrine greater than d-norepinephrine; intraocular pressure (IOP): l-epinephrine greater than dl-alpha-methyl-epinephrine greater than d-epinephrine greater than dl-alpha-methyl-norepinephrine greater than d-norepinephrine congruent to 1-norepinephrine. The pupil and the initial ocular hypertensive responses clearly demonstrated the phenomenon of stereoselectivity of adrenergic stimulants, in that the 1-form was relatively more potent than the d-form. However, such order of potency does not seem to hold for IOP. The apparent discrepancy and reversal of order of potency for IOP responses may be related to the hypothesis that the net ocular hypotensive effect of adrenergic agents is the summation of the initial hypertension and the delayed hypotension produced by these agents. It is anticipated that the results of the present study may improve our understanding of ocular pharmacology of adrenergic stereoisomers. The ability to separate the dose-response profiles of pupillary and IOP effects of these agents may have potential therapeutic significance and thus warrants further investigation in other species.
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Quantitative assessment of ocular norepinephrine concentration in the rabbit using liquid chromatography with electrochemical detection.
An assay technique that utilizes liquid chromatography with electrochemical detection to determine the norepinephrine (NE) concentration of the rabbit aqueous humor (AH) and iris-ciliary body (ICB) is discussed. NE concentration was monitored in control preparations as well as in experiments involving stimulation of the cervical sympathetic nerve (CSN) or 24 h following extirpation of the superior cervical ganglion. In 15 control rabbits, the baseline AH NE concentration was determined to be 7.2 and 7.8 ng/ml in the left and right eyes, respectively. Prolonged unilateral electrical stimulation of the CSN increased the AH NE concentration to 59.0 +/- 1.2 ng/ml on the stimulated side. Pretreatment with cocaine (12.5 mg/kg) and subsequent stimulation of the CSN increased the NE in the AH to 93.7 +/- 1.3 ng/ml on the stimulated side, and raised the baseline AH NE of the control (non-stimulated) side to 25.9 +/- 5.0 ng/ml. The baseline concentration of NE in the ICB was 5.4 +/- 0.8 micrograms/g. 24 h after a unilateral removal of the superior cervical ganglion, the NE content of the ICB was depleted by more than 90% in the ganglionectomized eye with no apparent change in the level of NE in the AH. The accurate analysis of catecholamines in the AH, ICB and other parts of the eye may be useful in providing information as to the extent of innervation and the possible role of sympathetic nerve supply in the overall control of AH dynamics.(ABSTRACT TRUNCATED AT 250 WORDS)
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Design of new contact lens for YAG laser filtering procedures.
A contact goniolens has been developed specifically for YAG laser filtering procedures both for use in unblocking failed surgical filtering procedures and for performing two-stage or one-stage YAG filtering procedures. The design concentrates the YAG energy and maintains a constant small angle with the cornea.
Contact Lenses↗
A physiological and pharmacological analysis of the electrodermal response in the rat.
Electrodermal responses (EDR) of the sympathetic-cholinergic sudomotor system were elicited in the footpads of the hindpaws of anesthetized rats. The most reactive CNS loci were caudal to the region of the posterior hypothalamus. Peripherally evoked responses were elicited by electrical stimulation of the decentralized tibial nerve. The amplitude of these evoked EDR was stable over time and both the centrally and peripherally elicited responses were frequency-dependent. Atropine (200 micrograms/kg) depressed the EDR elicited by both peripheral and central stimulation whereas hexamethonium (20 mg/kg) only inhibited the central EDR. Clonidine had no effect on the EDR evoked at the periphery but produced a significant dose-dependent depressant effect on the centrally evoked EDR; this effect was partially antagonized by yohimbine (0.75 mg/kg). It is suggested that the rat is a suitable species for the use of the sudomotor system in the investigation of adrenergic agents which are thought to have a central sympatho-inhibitory action.
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Acute intraocular pressure elevation produced by argon laser trabeculoplasty in the cynomolgus monkey.
The short-term effect of argon laser trabeculoplasty (ALT) was studied in a nonhuman primate model. The ALT treatment produced a consistent intraocular pressure elevation in the treated eye for eight hours. A statistically significant indomethacin-resistant increase in aqueous humor protein concentration was also observed. Morphologic observations using light microscopy and scanning and transmission electron microscopy revealed evidence of a fibrinous material covering the trabecular openings four hours after ALT. Cells and tissue debris appeared to be trapped in this fibrinlike net and may be the cause of the acute rise in IOP. Twenty-eight hours after ALT, the fibrin net was shown to be discontinuous, with fewer cells and less debris present. These acute morphologic alterations were not seen in control eyes or the laser-treated eyes observed later.
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Experimental YAG laser sclerostomy.
A Q-switched neodymium-YAG laser was used to produce a corneoscleral perforation in human cadaver eyes. A through-and-through incision could be created solely with the YAG-laser at peak pulse energies of 16 millijoules (mJ). The minimal total energy required for perforation was 3,312 mJ. However, "optimal" perforation, producing splitting along natural scleral cleavage planes, required 26,676 mJ. Scanning electron microscopy showed the perforations to be clean holes with little debris.
Cornea↗
Evidence for two distinct sympathoinhibitory bulbo-spinal systems.
Yohimbine hydrochloride (0.5 mg/kg, i.v.) caused a long-lasting potentiation of electrodermal (sympathetic-cholinergic) reflexes in intact anaesthetized and decerebrate unanaesthetized cats. Transection of the cervical spinal cord also resulted in an increased amplitude of the sudomotor reflex in unanaesthetized decerebrate preparations. Depletion of monoamines in the CNS by pretreatment with reserpine (5 mg/kg, i.p.) and alpha-methyl-p-tyrosine (2 X 300 mg/kg, i.p.) reduced the concentrations of norepinephrine, dopamine and serotonin to less than 93% of control levels in the thoracic spinal cord. In monoamine-depleted preparations, yohimbine no longer facilitated the reflex amplitude whereas the effect of spinal transection was not altered. These results suggest that there are two distinct sympathoinhibitory systems in the lower brain stem that converge on spinal sympathetic neurons, one of which is monoaminergic and one of which is not. Evidence for the baroreceptor-independent nature of these descending inhibitory systems is discussed.
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CNS adrenergic inhibition of parasympathetic oculomotor tone.
Inhibition of parasympathetic neural tone to the iris was produced by electrical stimulation of the afferent sciatic nerve, medullary reticular formation, and posterior hypothalamus in anesthetized cats in which only the parasympathetic nerves to the eye were intact. Stimulation of all 3 sites of activation produced a graded pupillary dilation and reduction of tonic nerve activity in the short ciliary nerves. Intravenous administration of the alpha-2-adrenoceptor antagonist, yohimbine hydrochloride, (0.03-1.0 mg/kg) produced a dose-dependent antagonism of the mydriasis elicited by activation of the ascending (sciatic nerve and medullary) mechanisms but did not block the pupillary dilation evoked by stimulation of the system descending from the hypothalamus. This differential action of yohimbine was confirmed directly by means of nerve recordings taken from the parasympathetic nerve to the eye. Depletion of CNS monoamines with reserpine and alpha-m-p-tyrosine reduced the norepinephrine concentration of the medulla and midbrain by 95% and 97%, respectively. In these depleted preparations, stimulation of the hypothalamus still produced the characteristic mydriasis and inhibition of parasympathetic tonic activity whereas activation of ascending mechanisms (sciatic or medullary) were no longer effective in producing these effects. Taken together, these results suggest that ascending parasympatho -inhibition is mediated by a monoamine (probably norepinephrine) and that inhibition descending from the hypothalamus is mediated by a non-monoaminergic mechanism.
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Analysis of CNS sympatho-inhibition produced by guanabenz.
The effects of guanabenz on several autonomic systems were observed in vagotomized, anesthetized cats with the aim of determining, in a quantitative sense, the degree to which guanabenz produces a clonidine-like central nervous system action. Guanabenz given as a single dose (50 micrograms/kg i.v.) produced a transient hypertension associated with a more sustained bradycardia and depression of centrally (hypothalamic) evoked electrodermal responses (EDR). Increasing cumulative doses of guanabenz (3-1000 micrograms/kg i.v.) also resulted in a dose-related depression of EDR amplitude, transient hypertension followed by hypotension, sustained bradycardia, and mydriasis. All responses were antagonized by pretreatment with yohimbine (0.5 mg/kg i.v.). The ED50 for depression of the centrally evoked EDR was in the range of 50-100 micrograms/kg i.v. in the non-pretreated preparations. Guanabenz (100 micrograms/kg i.v.) was shown to be devoid of significant ganglionic blocking properties. These experiments suggest that guanabenz acts like clonidine in the CNS and that an alpha 2-adrenergic inhibitory mechanism is involved in its myriad of central autonomic effects.
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Use of a sympathetic-cholinergic system in the analysis of sympatho-inhibition produced by clonidine and some congeneric derivatives of clonidine.
The effects of clonidine and five analogs of clonidine were tested with regard to their ability to depress centrally and peripherally evoked electrodermal responses (EDR) in control cats, as well as in animals pretreated with yohimbine hydrochloride. With the exception of St-91, all of the clonidine-like substances selectively reduced the amplitude of centrally (hypothalamic) evoked responses in a dose-dependent fashion. Clonidine was found to have no significant inhibitory effect at the level of the sympathetic ganglion. The order of central nervous system sympatho-inhibitory potency of these compounds was clonidine (St-155) greater than St-375 greater than St-606 greater than St-600 greater than St-608 much much greater than St-91. Prior treatment with yohimbine hydrochloride (0.5 mg/kg i.v.) antagonized the depressant effect of all of these drugs. These results indicate that clonidine and the clonidine congeners tested (with the exception of St-91) all produce sympatho-inhibition by an action on a CNS alpha-adrenergic mechanism and demonstrate the usefulness of this electrodermal model system for the analysis of drugs affecting central sympathetic reactivity.
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