H-7 Effect on Outflow Facility after Trabecular Obstruction Following Long-Term Echothiophate Treatment in Monkeys

Gabelt, B’Ann T.; Hennes, E.A.; Seeman, Jennifer L.; Tian, Baohe; Kaufman, Paul L.

doi:10.1167/iovs.04-0083

Cited by 19 publications

(8 citation statements)

References 13 publications

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“…In support of this role, when human or monkey organ cultured anterior segments were perfused with the Heparin II binding domain or a PRARI peptide that activates α4β1 integrin signaling, outflow facility was increased (Santas et al, 2003; Gonzalez et al, 2009) and an expansion of the TM reminiscent of actin disrupting agents was observed (Gabelt et al, 2004, 2006; Schwinn et al, 2010). Interestingly, expression of the α4 integrin subunit is increased in the ONH in glaucomatous eyes (Morrison, 2006).…”

Section: Biological Processes Regulated By Integrinsmentioning

confidence: 97%

The role of integrins in glaucoma

Filla

Faralli

Peotter

et al. 2017

Experimental Eye Research

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Integrins are a family of heterodimeric transmembrane receptors that mediate adhesion to the extracellular matrix (ECM). In addition to their role as adhesion receptors, integrins can act as “bidirectional signal transducers” that coordinate a large number of cellular activities in response to the extracellular environment and intracellular signaling events. This bidirectional signaling helps maintain tissue homeostasis. Dysregulated bidirectional signaling, however, could trigger the propagation of feedback loops that can lead to the establishment of a disease state such as glaucoma. Here we discuss the role of integrins and bidirectional signaling as they relate to the glaucomatous phenotype with special emphasis on the αvβ3 integrin. We present evidence that this particular integrin may have a significant impact on the pathogenesis of glaucoma.

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Section: Biological Processes Regulated By Integrinsmentioning

confidence: 97%

The role of integrins in glaucoma

Filla

Faralli

Peotter

et al. 2017

Experimental Eye Research

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“…The drug is available under several trade names such as phospholine iodide. Adverse effects include muscle spasm and other systemic effects [112]. …”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

et al. 2013

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Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases.

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“…In nonhuman primate eyes, long-acting cholinesterase inhibitors such as echothiophate iodide have been shown to cause an increase in IOP, collapse and densification of the trabecular meshwork, alterations in the shape and orientation of Schlemm’s canal and the ciliary muscle, and discontinuity between ciliary muscle bundles and trabecular beams (Gabelt, Hennes, Seeman, Tian and Kaufman, 2004;Lutjen-Drecoll and Kaufman, 1986). Chronic echothiophate use also results in a decreased accommodative response to pilocarpine (Croft, Kaufman, Erickson-Lamy and Polansky, 1991).…”

Section: Introductionmentioning

confidence: 99%

Autonomic drugs and the accommodative system in rhesus monkeys

Ostrin

Glasser

2010

Experimental Eye Research

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Accommodation and pupil constriction result from parasympathetic stimulation from the Edinger-Westphal (EW) nucleus of the midbrain resulting in release of acetylcholine at the neuromuscular junctions of the ciliary muscle and iris. Cholinergic and adrenergic drugs can be applied topically to evaluate the effects on the pupil and accommodative system without input from the EW nucleus. This study is directed at characterizing how topical low dose echothiophate, an anti-cholinesterase inhibitor (i.e., an indirect cholinergic agonist), epinephrine, an adrenergic agonist, and timolol maleate, a beta adrenergic antagonist, affect pupil diameter, resting refraction and accommodative amplitude and dynamics in rhesus monkeys. The effects of 0.015% echothiophate, 2% epinephrine, 0.5% timolol maleate and saline on pupil diameter and resting refraction were measured in one eye each of four normal rhesus monkeys for 60-90 minutes following topical instillation. Pupil diameter was measured with infrared videography and refraction was measured with a Hartinger coincidence refractometer. Effects on static and dynamic EW stimulated accommodation were studied in three iridectomized monkeys (ages 5, 6 and 12 years) with permanent indwelling stimulating electrodes in the EW nucleus. Dynamic accommodative responses were measured with infrared photorefraction for increasing current amplitudes before and during the course of action of the pharmacological agents. Echothiophate caused a significant decrease in pupil diameter of 3.07 ± 0.65 mm (mean ± SEM, p < 0.01), and a myopic shift in resting refraction of 1.30 ± 0.39 D (p < 0.05) 90 minutes after instillation. Epinephrine caused a 2.76±0.38 mm (p < 0.01) increase in pupil diameter with no change in resting refraction 60 minutes after instillation. Timolol maleate resulted in no significant change in either pupil diameter or resting refraction 60 minutes after instillation. There was no significant change in maximum EW stimulated accommodative amplitude after any agent tested. The amplitude vs. peak velocity relationship for accommodation was significantly different after echothiophate and timolol maleate, and for disaccommodation after echothiophate, epinephrine and timolol maleate. In conclusion, when tested objectively in anesthetized monkeys, epinephrine and timolol maleate did not alter resting refraction or accommodative amplitude, but did have small, significant affects on accommodative dynamics. This suggests that there is an adrenergic component to the accommodative system. Low dose echothiophate had significant effects on pupil diameter and resting refraction, with only small effects on the dynamics of the accommodative response.

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H-7 Effect on Outflow Facility after Trabecular Obstruction Following Long-Term Echothiophate Treatment in Monkeys

Abstract: H-7 can enhance OF in the presence of trabecular obstruction produced by long-term ECHO treatment. This suggests that H-7 may be useful in treating glaucoma, even in the presence of accumulated plaque material that has been described previously.

Cited by 19 publications

References 13 publications

The role of integrins in glaucoma

The role of integrins in glaucoma

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

Autonomic drugs and the accommodative system in rhesus monkeys

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