Differential smooth muscle-like contractile properties of trabecular meshwork and ciliary muscle

Lepple-Wienhues, Albrecht; Stahl, Frank; Wiederholt, Michael

doi:10.1016/0014-4835(91)90141-z

Cited by 90 publications

(58 citation statements)

References 16 publications

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“…1), which were inhibitable by atropine, demonstrating the presence of muscarinic receptors [29, 31]. The induction of force could be increased by application of physostigmin, a reversible anticholinesterase inhibitor, demonstrating the presence of acetylcholinesterase in trabecular meshwork cells.…”

Section: Contractility Measurementsmentioning

confidence: 99%

“…Using a purpose-built force-length transducer similar to that described by Brutsaert et al [30], the isometric force of the strips could be monitored for a period of several hours after an equilibration period of approximately 1 h [29, 31, 32, 33, 34]. …”

Section: Contractility Measurementsmentioning

confidence: 99%

“…Application of high-potassium external solution is a standard procedure for inducing smooth-muscle contraction [35, 36]. In trabecular meshwork, application of 120 mmol/l KCl evoked a contraction that was biphasic but corresponded to only 19% of the response attainable by acetylcholine [29]. Part of the KCl response was blockable by atropine.…”

Section: Contractility Measurementsmentioning

confidence: 99%

“…For the contractility measurements, bovine eyes were dissected and strips of trabecular meshwork and ciliary muscle prepared according to established methods [29]. Using a purpose-built force-length transducer similar to that described by Brutsaert et al [30], the isometric force of the strips could be monitored for a period of several hours after an equilibration period of approximately 1 h [29, 31, 32, 33, 34].…”

Section: Contractility Measurementsmentioning

confidence: 99%

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Regulation of Trabecular Meshwork Contractility

Stumpff

Wiederholt²

2000

Ophthalmologica

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Ample evidence supports the theory that trabecular meshwork possesses smooth-muscle-like properties. Trabecular meshwork cells express a large number of transporters, channels and receptors, many of which are known to regulate smooth-muscle contractility. It has been shown that trabecular meshwork can be induced to contract and relax in response to pharmacological agents. In the model of the bovine eye, confirmed in some cases by experiments on primates, agents that contract trabecular meshwork reduce outflow. On the cellular level, this is coupled with depolarization and a rise in intracellular calcium. Relaxation of trabecular meshwork, on the other hand, appears to be coupled to a stimulation of the maxi-K channel, inducing hyperpolarization and a closure of L-type calcium channels. No significant differences between cells from a human and a bovine source emerged, either in classical measurements of membrane voltage, in measurements of intracellular calcium or patch-clamp experiments. Thus, pharmacological agents that relax trabecular meshwork seem promising candidates for further research – the ultimate goal being an improvement of glaucoma therapy in humans.

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Section: Contractility Measurementsmentioning

confidence: 99%

Section: Contractility Measurementsmentioning

confidence: 99%

Section: Contractility Measurementsmentioning

confidence: 99%

Section: Contractility Measurementsmentioning

confidence: 99%

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Regulation of Trabecular Meshwork Contractility

Stumpff

Wiederholt²

2000

Ophthalmologica

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“…Recently, we showed that an electrogenic Na'-HCOT cotransport is absent in bovine trabecular meshwork cells (6). Thus this transporter may serve as a tool to differentiate between ciliary muscle cells and cells derived from trabecular meshwork, which has likewise proven to be contractile (21). …”

Section: Discussionmentioning

confidence: 99%

Electrogenic sodium-bicarbonate cotransport in human ciliary muscle cells

Stahl

Lepple-Wienhues

Kuppinger

et al. 1992

American Journal of Physiology-Cell Physiology

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We investigated membrane voltage and intracellular pH (pHi) in cultured human ciliary muscle cells using a cell line (H7CM) and primary-cultured human ciliary muscle cells. 1) Resting potential was 58.9 +/- 1.0 mV in H7CM cells and 61.9 +/- 1.4 mV in primary cultures. The following data are from H7CM cells, but results from primary cultures were basically similar. 2) In HCO3(-)-CO2-buffered solution, removal of extracellular sodium resulted in a depolarization [change in membrane resistance (delta V) = 31.3 +/- 2.8 mV] that was less marked in the absence of HCO3(-)-CO2 (delta V = 0.5 +/- 2.6 mV) and reduced by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (delta V = 19.3 +/- 1.9 mV). 3) Removal of extracellular HCO3(-)-CO2 led to a depolarization (delta V = 13.2 +/- 0.8 mV) that was abolished in the absence of extracellular sodium and inhibited by DIDS. 4) Intracellular alkalinization led to a depolarization (delta V = 24.7 +/- 2.3 mV), and intracellular acidification resulted in a hyperpolarization (delta V = 9.4 +/- 1.1 mV) that was inhibited by DIDS and dependent on extracellular HCO3(-)-CO2 and sodium. 5) pHi backregulation after an acid load occurred in both the presence and absence of extracellular bicarbonate but not in the absence of extracellular sodium. Our data are consistent with an electrogenic Na(+)-HCO3- cotransport in human ciliary muscle cells, which is activated by intracellular acidification.

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Effects of Protein Kinase Inhibitor, HA1077, on Intraocular Pressure and Outflow Facility in Rabbit Eyes

Honjo

Inatani²,

Kido³

et al. 2001

Arch Ophthalmol

143

116

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To elucidate the roles of protein kinase in regulating the intraocular pressure (IOP) and outflow facility in rabbit eyes. Materials and Methods: A protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-homopiperazine (HA1077), was used. The IOP and the outflow facility were measured before and after topical, intracameral, or intravitreal administration of HA1077 in rabbits. Western blot analysis was performed to detect the 20-kd light chain of myosin in human trabecular meshwork (TM) cells and bovine ciliary muscle (CM) tissues. The cell morphologic condition and distribution of actin filaments and vinculin in TM cells were studied using cell biology techniques. Carbachol-induced contraction of isolated bovine CM strips following administration of HA1077 was examined in a perfusion chamber. Results: In rabbit eyes, the administration of HA1077 resulted in a significant decrease in IOP in a dosedependent manner. An increased outflow facility was also observed. Western blot analysis revealed the presence of 20-kd light chain of myosin in human TM cells and bovine CM tissues. In cultured human TM cells, exposure to HA1077 disrupted actin bundles and impaired focal adhesion formation. In addition HA1077 showed relaxation of bovine CM strips. Conclusions: Use of HA1077 caused a reduction in IOP and an increase in the outflow facility. The results of in vitro experiments suggest that the IOP-lowering effects of HA1077 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction. The results of these studies suggested that protein kinase inhibitors have the potential to be developed into a treatment modality for glaucoma.

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Differential smooth muscle-like contractile properties of trabecular meshwork and ciliary muscle

Cited by 90 publications

References 16 publications

Regulation of Trabecular Meshwork Contractility

Regulation of Trabecular Meshwork Contractility

Electrogenic sodium-bicarbonate cotransport in human ciliary muscle cells

Effects of Protein Kinase Inhibitor, HA1077, on Intraocular Pressure and Outflow Facility in Rabbit Eyes

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