The Structure of the Trabecular Meshwork, Its Connections to the Ciliary Muscle, and the Effect of Pilocarpine on Outflow Facility in Mice

Overby, Darryl R.; Bertrand, Jacques; Schicht, Martin; Paulsen, Friedrich; Stamer, W. Daniel; Lütjen–Drecoll, Elke

doi:10.1167/iovs.13-13699

Cited by 92 publications

(96 citation statements)

References 33 publications

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“…These drugs increase conventional outflow and decrease IOP [136,137] by inducing ciliary muscle contraction, increasing SC lumen area, in turn allowing for increased aqueous fluid transport across SC endothelial cells [138]. As previously mentioned, elastin fibers are responsible for the connection of the ciliary body to SC and associated muscle contractions.…”

Section: Traditional Topical Medications In the Management Of Glaucomamentioning

confidence: 99%

“…As previously mentioned, elastin fibers are responsible for the connection of the ciliary body to SC and associated muscle contractions. The ciliary muscles express cholinergic nerve terminals facilitating contraction, and it is presumed that the muscle is pulled back again by a recoil of the elastin net [137,139].…”

Section: Traditional Topical Medications In the Management Of Glaucomamentioning

confidence: 99%

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Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

O’Callaghan

Cassidy

Humphries

2017

Expert Opinion on Therapeutic Targets

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Introduction:Ocular hypertension in open-angle glaucoma is caused by a reduced rate of removal of aqueous humour (AH) from the eye, with the majority of AH draining from the anterior chamber through the conventional outflow pathway, comprising the trabecular meshwork (TM) and Schlemm's Canal. Resistance to outflow is generated, in part, by the extracellular matrix (ECM) of the outflow tissues. Current pressure-lowering topical medications largely suppress AH production, or enhance its clearance through the unconventional pathway. However, therapies targeting the ECM of the conventional pathway in order to decrease intraocular pressure have become a recent focus of attention. Areas covered: We discuss the role of ECM of the TM in outflow homeostasis and its relevance as a target for glaucoma therapy, including progress in development of topical eye formulations, together with gene therapy approaches based on inducible, virally-mediated expression of matrix metalloproteinases to enhance aqueous outflow. Expert opinion: There remains a need for improved glaucoma medications that more specifically act upon sites causative to glaucoma pathogenesis. Emerging strategies targeting the ECM of the conventional outflow pathway, or associated components of the cytoskeleton of TM cells, involving new pharmacological formulations or genetically-based therapies, are promising avenues of future glaucoma treatment. ARTICLE HISTORY

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Section: Traditional Topical Medications In the Management Of Glaucomamentioning

confidence: 99%

Section: Traditional Topical Medications In the Management Of Glaucomamentioning

confidence: 99%

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

O’Callaghan

Cassidy

Humphries

2017

Expert Opinion on Therapeutic Targets

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“…This movement releases tension on the zonules of the crystalline lens, thereby enabling accommodation (Overby et al, 2014). Posteriorly, the ciliary muscle tendons insert into the choroidal elastic network and to the adventitial sheaths of the pars plana and choroidal vessels (Tamm and Lütjen-Drecoll, 1996;Lütjen-Drecoll, 2006).…”

Section: Anatomy Of the Accommodative Apparatusmentioning

confidence: 99%

“…However, the circular and longitudinal portions of the ciliary muscle appear to have different roles in the eye. While the contraction of the circular part of the ciliary muscle enables accommodation, the contraction of the longitudinal muscle, opens the trabecular meshwork, is transmitted directly to the trabecular meshwork elastic network, and thereby to Schlemm's canal endothelium, expanding the area of filtration, and ultimately lowering IOP (Costagliola et al, 2009;Overby et al, 2014).…”

Section: Modulation Of Pupil Responses By the Autonomic Nervous Systemmentioning

confidence: 99%

“…Although changes in the ciliary muscle tone may directly influence intratrabecular spaces and the patency of the collapsible Schlemm's canal (Gil et al, 1997;Wiederholt et al, 2000), recent experiments have shown that the trabecular meshwork is a contractile tissue itself, with smooth muscle-like properties, and is actively involved in aqueous humour outflow (Wiederholt et al, 2000;Overby et al, 2014). In humans this area of the anterior segment is enriched with cholinergic and nitrergic nerve terminals that could induce contraction and relaxation of the trabecular meshwork and Schlemm's canal cells influencing the geometry of the intratrabecular spaces and modulating the amount of aqueous humor entering Schlemm's canal (Selbach et al, 2000;Wiederholt al., 2000).…”

Section: Introductionmentioning

confidence: 99%

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The Influence of the Autonomic Nervous System on the Human Choroid

Sander¹

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v AbstractThe impact of myopia is greater than just its optical consequences and in severe cases it can lead to a loss of vision. It is a highly prevalent eye disorder, with about one third of the population worldwide affected by this refractive error. Despite extensive research, the pathogenesis of myopia is still only partially understood. An improved knowledge of mechanisms underlying myopia is critical to developing new therapies to prevent myopia or to slow its progression.Although there is no fully effective and satisfactory myopia control treatment available, growing evidence has suggested that the choroid has a passive or active role in the regulation of eye growth and refractive error development. Numerous human and animal studies have shown that the retina can be moved forward or backward towards the image plane through changes in choroidal thickness, and these changes are likely to be associated in the longer term with eye growth and the development of refractive errors. As the choroid receives a rich innervation from the autonomic nervous system, many previous animal studies have utilized pharmacological agents and neurotoxins to elucidate the possible role of muscarinic signaling in the regulation of choroidal thickness, but only a few studies have investigated this issue in humans. An improved understanding of the mechanisms that control choroidal thickness may be important in developing new therapies for combating the development and progression of myopia.The research described in the thesis aimed to investigate the role of the autonomic nervous system in the control of choroidal thickness, axial length and the morphology In a series of experiments, we have confirmed that in humans under normal visual conditions, the parasympathetic nervous system is involved in the short-term regulation of subfoveal and parafoveal choroidal thickness, axial length and the morphology of the anterior sclera. The muscarinic blocker homatropine caused a significant subfoveal and parafoveal choroidal thickening, shortening of axial length, an enlargement of Schlemm's canal area and an increase in thickness of the conjunctival/episcleral complex. On the other hand, no notable changes in ocular parameters, except a decrease in the thickness of the conjunctival/episcleral tissues were found after instillation of the sympathomimetic drug phenylephrine.In an attempt to further improve our understanding of the myopigenic mechanisms influencing the thickness of the choroid in humans, we investigated the short-term influence of mixed interventions (positive and negative lens-imposed defocus / 2% homatropine) on choroidal thickness and axial length in emmetropic and myopic subjects. Homatropine prevented choroidal thinning in response to hyperopic defocus.This finding is consistent with the anti-myopia effects of muscarinic blockers and supports the potential importance of hyperopic defocus in the development of human myopia. By contrast, co-administration of homatropine with myopic defocus did not enhance the thicken...

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Effect of Pilocarpine Hydrochloride on the Schlemm Canal in Healthy Eyes and Eyes With Open-Angle Glaucoma

et al. 2016

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IMPORTANCEThe in vivo effect of pilocarpine hydrochloride on the Schlemm canal may help explain its pharmacologic mechanism of action and better indicate its clinical use.OBJECTIVE To investigate the effect of pilocarpine on the structure of the Schlemm canal in vivo in healthy eyes and eyes with glaucoma. DESIGN, SETTING, AND PARTICIPANTSIn this case-control study, healthy individuals and patients with open-angle glaucoma were prospectively enrolled between September 1, 2013, and June 30, 2014, after a complete ophthalmologic examination at a tertiary glaucoma referral practice. Eighty-one serial, horizontal, enhanced depth imaging optical coherence tomographic B-scans (interval between B-scans, approximately 35 μm) of the nasal corneoscleral limbus were performed before and 1 hour after topical administration of pilocarpine, 1%, in 1 eye of healthy volunteers and pilocarpine, 2%, in 1 eye of patients with glaucoma. Fifty B-scans in the overlapping area (circumferential length, approximately 1.7 mm) between the 2 sets of serial scans (before and after pilocarpine administration) were selected for analysis based on the structures of aqueous and blood vessels as landmarks. The cross-sectional area of the Schlemm canal was measured in each selected B-scan. Volume of the Schlemm canal was calculated using commercially available 3-dimensional reconstruction software. MAIN OUTCOMES AND MEASURES Mean cross-sectional area of the Schlemm canal.RESULTS Enhanced depth imaging optical coherence tomographic scans of the Schlemm canal were performed successfully before and after administration of pilocarpine, 1%, in 9 healthy eyes (9 individuals) and pilocarpine, 2%, in 10 eyes with glaucoma (10 patients) (mean [SD] age, 31.9 [7.8] and 68.7 [13.2] years, respectively). Following pilocarpine administration, mean (SD) intraocular pressure decreased from 14.3 (1.3) to 13.7 (1.1) mm Hg in healthy eyes (P = .004) and from 17.5 (6.0) to 16.6 (6.1) mm Hg in eyes with glaucoma (P = .01). The mean (SD) cross-sectional area of the Schlemm canal increased by 21% (4667 [1704] to 5647 [1911] μm 2 ) in healthy eyes (P < .001) and by 24% (3737 [679] to 4619 [692] μm 2 ) in eyes with glaucoma (P < .001) (mean difference in percent increase, 2.2%; 95% CI, -8.5% to 12.9%). The mean (SD) volume of the Schlemm canal in the overlapping area increased from 8 004 000 (2 923 000) to 9 685 000 (3 277 000) μm 3 in healthy eyes (P < .001) and from 6 468 000 (1 170 000) to 7 970 000 (1 199 000) μm 3 in eyes with glaucoma (P < .001).CONCLUSIONS AND RELEVANCE These data suggest that pilocarpine expands the Schlemm canal in eyes with and without glaucoma. No differences in the effect were identified between the 2 groups. Enhanced depth imaging optical coherence tomography may be useful in investigating the effect of pharmacologic agents on the Schlemm canal.

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The Structure of the Trabecular Meshwork, Its Connections to the Ciliary Muscle, and the Effect of Pilocarpine on Outflow Facility in Mice

Cited by 92 publications

References 33 publications

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

The Influence of the Autonomic Nervous System on the Human Choroid

Effect of Pilocarpine Hydrochloride on the Schlemm Canal in Healthy Eyes and Eyes With Open-Angle Glaucoma

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