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Paul L Kaufman - One of the best experts on this subject based on the ideXlab platform.
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age related posterior Ciliary Muscle restriction a link between trabecular meshwork and optic nerve head pathophysiology
Experimental Eye Research, 2017Co-Authors: Mary Ann Croft, Elke Lutjendrecoll, Paul L KaufmanAbstract:Abstract The Ciliary Muscle plays a major role in controlling both accommodation and outflow facility in primates. The Ciliary Muscle and the choroid functionally form an elastic network that extends from the trabecular meshwork all the way to the back of the eye and ultimately attaches to the elastic fiber ring that surrounds the optic nerve and to the lamina cribrosa through which the nerve passes. The Ciliary Muscle governs the accommodative movement of the elastic network. With age Ciliary Muscle mobility is restricted by progressively inelastic posterior attachments and the posterior restriction makes the contraction progressively isometric; placing increased tension on the optic nerve region. In addition, outflow facility also declines with age and limbal corneoscleral contour bows inward. Age-related loss in Muscle movement and altered limbal corneoscleral contour could both compromise the basal function of the trabecular meshwork. Further, recent studies in non-human primates show that the central vitreous moves posteriorly all the way back to the optic nerve region, suggesting a fluid current and a pressure gradient toward the optic nerve. Thus, there may be pressure and tension spikes on the optic nerve region during accommodation and these pressure and tension spikes may increase with age. This constellation of events could be relevant to glaucomatous optic neuropathy. In summary, our hypothesis is that glaucoma and presbyopia may be literally linked to each other, via the choroid, and that damage to the optic nerve may be inflicted by accommodative intraocular pressure and choroidal tension “spikes”, which may increase with age.
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Effect of nitric oxide compounds on monkey Ciliary Muscle in vitro.
Experimental eye research, 2010Co-Authors: B'ann T. Gabelt, Paul L Kaufman, Carol A. RasmussenAbstract:The effects of various nitric oxide compounds and their inhibitors on monkey Ciliary Muscle contraction in vitro were investigated in both the longitudinal and circular vectors. The responses to nitric oxide compounds in carbachol precontracted Ciliary Muscle consisted of an initial relaxation often followed by recovery to near carbachol precontracted levels while the compound was still present. Sodium nitroprusside produced the greatest relaxation responses (nearly 100% relaxation in both vectors at 10(-3) M). The highest concentrations of isosorbide dinitrate (10(-4) M) and L-arginine (10(-3) M) produced relaxation responses of approximately 50% in both vectors. 8-Bromo cyclic GMP produced the smallest relaxation responses (25-35%). Nitric oxide synthase inhibition enhanced carbachol contraction up to 20% in the longitudinal but not the circular vector. Phosphodiesterase inhibition did not further enhance the relaxation response to L-arginine. Guanylate cyclase inhibition partially attenuated the relaxation response to sodium nitroprusside. Nitric oxide generating compounds were effective in relaxing precontracted monkey Ciliary Muscle in vitro. Endogenous production of nitric oxide is likely involved in the regulation of the contractile response in monkey Ciliary Muscle. Nitric oxide generating compounds may have potential value in therapeutic areas where modulation of Ciliary Muscle tension is desirable.
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morphologic indication for proprioception in the human Ciliary Muscle
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Cassandra Flugelkoch, Paul L Kaufman, Winfried Neuhuber, Elke LutjendrecollAbstract:The complex process of accommodation in primates is mediated by the Ciliary Muscle that, by configurational changes of its three portions, moves anterior inwardly, thereby influencing the tension of the zonular fibers and thus the shape of the lens. This complicated process is reflected in the structure of the Ciliary Muscle itself. Unlike smooth Muscle seen in vessels or gut wall, the Ciliary Muscle has tendons for anterior and posterior attachment and the Muscle cells exhibit a regular array of dense bands and dense bodies resembling Z-stripes1,2 and histochemical staining qualities, similar to striated Muscle.3 The innervation of the Ciliary Muscle also differs from that of vessel or gut wall smooth Muscle. Ciliary Muscle cells are extremely densely innervated by cholinergic parasympathetic terminals of the oculomotor nerve1,4–6 and lack gap junctions.2,7–9 Additionally, there are large numbers of intrinsic nerve cells staining for NADPH diaphorase and nitric oxide synthase (NOS).10 These cells are present only in those primate species with a well-developed fovea centralis.11 In human eyes approximately 900 such cells are found in total, localized only in the inner circular and reticular portions of the Ciliary Muscle, where they are assumed to induce relaxation of the Muscle cells.10 In contrast to this prominent efferent innervation, sparse data exist about the Muscle's afferent neurons. Large nerve endings are present in the scleral spur of human eyes, where the tendons of the outer longitudinal Ciliary Muscle portion insert.12,13 Also within the trabecular meshwork, where tendons of the Ciliary Muscle radiate to form connections between the Muscle and the aqueous humor outflow region, afferent terminals staining for calcitonin gene-related peptide (CGRP) and substance P (SP) are often found in contact with elastic fibers.13 Similar results have also been obtained for the monkey eye.14 Morphologically, these nerve endings resemble the afferent terminals of visceral mechanoreceptors measuring stretch or distension. The presence of afferent nerve endings perceiving tension or shearing forces in smooth Muscle is not unusual. In the gastrointestinal tract, abundant endings have been located in the connective tissue between the two Muscle layers of the muscular wall (for reviews see Refs. 15–17). In other tissues such as vasculature (for reviews see Refs. 18–20), periodontal tissue (for reviews see Refs. 21, 22), urogenital,23,24 and respiratory tract (for reviews see Refs. 25–28), afferent endings representing proprioreceptors have been described. In most cases the putative muscular mechanoreceptors express the calcium-binding proteins calretinin and calbindin.16,29–34 Within the vagal mechanosensory terminals in the tunica muscularis of the esophagus (the intraganglionic laminar endings) and in vagal bronchopulmonary and skeletomuscular mechanosensors, the presence of vesicular glutamate transporter 2 (VGLUT 2) has been detected.16 The complex process of Ciliary Muscle contraction and its significance for dynamic, precise, and rapid visual focus on objects at any distance suggests the existence of afferent proprioreception to modulate the rapid and controlled adjustment of the fine Muscle movements needed for efficient accommodation and disaccommodation. In the present study, we have, therefore, examined the entire human Ciliary Muscle and its posterior and anterior tendons with respect to proprioreceptive nerve endings using immunohistochemical staining methods applied to sections cut in different planes and to various wholemount preparations. Additionally, selected specimens fixed in glutaraldehyde were investigated ultrastructurally.
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aqueous humor dynamics and trabecular meshwork and anterior Ciliary Muscle morphologic changes with age in rhesus monkeys
Investigative Ophthalmology & Visual Science, 2003Co-Authors: B'ann T. Gabelt, Paul L Kaufman, Elke Lutjendrecoll, Johannes GottankaAbstract:PURPOSE. To determine in rhesus monkeys the age-dependence of uveoscleral outflow (Fu) and morphology of the trabecular meshwork (TM) and anterior Ciliary Muscle (CM). METHODS. Intraocular pressure (IOP) was measured by Goldmann applanation tonometry in monkeys under ketamine anesthesia. After anterior chamber cannulation under pentobarbital anesthesia, aqueous humor formation (AHF), anterior chamber volume, trabecular outflow, and Fu were determined isotopically. The CM and TM were examined by light and electron microscopy. RESULTS. IOP increased significantly with age in monkeys aged 3 to 29 years. AHF and anterior chamber volume were unchanged. Fu was decreased, and trabecular outflow increased in monkeys aged 25 to 29 years compared with the remaining monkeys. Morphologically, there was a significant increase in the thickness of the elastic fibers of the trabeculum ciliare covering the anterior tips of the CM, and an increase in extracellular material between the Muscle tips. The number of TM cells decreased with age, whereas the amount of fibrillar material and sheath-derived plaques increased. This increase was less pronounced in the middle filtering portion of the cribriform region than in the anterior and posterior portions. CONCLUSIONS. The decline in Fu in very old rhesus monkeys with normal IOP parallels that seen in normotensive aging humans. This may be correlated with thickening of the elastic fiber sheath in the CM tips in addition to other morphologic changes. The TM findings are analogous to those in the aging human eye and are consistent with the age-related decrease in outflow facility reported in both humans and monkeys. (Invest Ophthalmol Vis Sci. 2003;44:2118 ‐2125) DOI:10.1167/ iovs.02-0569 I
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h 7 increases trabecular facility and facility after Ciliary Muscle disinsertion in monkeys
Investigative Ophthalmology & Visual Science, 1999Co-Authors: Baohe Tian, B'ann T. Gabelt, Jennifer A Peterson, Julie A Kiland, Paul L KaufmanAbstract:PURPOSE To determine the effects of the serine-threonine kinase inhibitor H-7 on total outflow facility in iridectomized + Ciliary Muscle (CM)- disinserted, and on trabecular facility in normal, monkey eyes. METHODS Total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber. Trabecular outflow facility was determined from accumulation in blood of intracamerally infused radioiodinated albumin at two intraocular pressure levels. RESULTS Three-hundred micromoles of intracameral H-7 doubled facility in iridectomized + CM- disinserted monkey eyes and contralateral iridectomized-only eyes. Four 5-microl drops of 400 mM H-7 applied topically followed 2 hours later by anterior chamber exchange for 10 minutes and intracameral infusion for 90 minutes with 100 microM H-7 increased trabecular and total outflow facility by 135%+/-29% and 105%+/-35% (n 5, P < 0.01, P < 0.05), respectively, compared with contralateral vehicle-treated eyes. CONCLUSIONS H-7 increases trabecular outflow facility in monkeys by a mechanism independent of the CM, presumably acting directly on the trabecular meshwork.
Donald O Mutti - One of the best experts on this subject based on the ideXlab platform.
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morphological Ciliary Muscle changes associated with form deprivation induced myopia
Experimental Eye Research, 2020Co-Authors: Andrew D Pucker, Ashley R Jackson, Kirk M Mchugh, Donald O MuttiAbstract:Abstract Myopic children have larger Ciliary Muscles than non-myopic children, suggesting that the Ciliary Muscle may have an impact on or be affected by refractive error development. The guinea pig represents an attractive model organism for myopia development research. The purpose of the study was to investigate whether form deprivation-induced myopia in one or more strains of guinea pig causes thickening of the Ciliary Muscle as seen in human myopia. Thirty-nine guinea pigs were bred from in-house progenitors obtained from Cincinnati Children's Hospital (Cincinnati) and the United States Army (Strain 13). At 2–4 days of age the right eyes of animals were exposed to form deprivation for 7 days while the fellow eyes served as controls. Refractive error was determined with retinoscopy while vitreous chamber depth (VCD) and axial length (AL) were determined with A-scan ultrasound. Ciliary Muscle characteristics (Ciliary Muscle length, cross-sectional area, volume, cell number, cell size, and smooth Muscle actin concentration) were determined histologically with antibody labeling and analyzed according to whether the animal developed axial myopia (anisometropia > −2.00 D with VCD and/or AL differences > 0.1 mm) or was unresponsive. This analysis method yielded four groups with Group 1 having no induced myopia but with axial elongation (n = 11), Group 2 having myopia without vitreous or axial elongation (n = 8), Group 3 having myopia with either vitreous or axial elongation (n = 11), and Group 4 having myopia with both vitreous and axial elongation (n = 8). There were no post-treatment inter-ocular differences between strains or for the overall group of animals for any Ciliary Muscle variable; however, a higher response group number in multivariate ordinal regression was related to having a treated compared to fellow eye that had a lower smooth Muscle actin concentration (p = 0.006), with a shorter Ciliary Muscle length (p = 0.042), and a less oblate eye shape (p = 0.010). Guinea pig Ciliary Muscle length and smooth Muscle actin concentration were significantly less in the treated eyes of axially myopic animals suggesting that 7 days of form deprivation induced Ciliary Muscle cellular atrophy or inhibited Ciliary Muscle growth. Form deprivation myopia in the guinea pig does not result in the increase in Ciliary Muscle thickness associated with human juvenile and adult myopia.
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Ciliary Muscle cell changes during guinea pig development
Investigative Ophthalmology & Visual Science, 2015Co-Authors: Andrew D Pucker, Ashley R Jackson, Hugh J Morris, Andrew J Fischer, Kirk M Mchugh, Donald O MuttiAbstract:The Ciliary body is an important ocular structure because it produces aqueous humor, controls aqueous humor drainage (uveoscleral outflow), and produces accommodation.1 The ability to accommodate (changing the eye's refractive focus) results from flexure of the Ciliary Muscle within the Ciliary body.1 The Ciliary Muscle runs parallel to the sclera, and its anterior attachment is to the scleral spur/trabecular meshwork while its posterior attachment is to the stroma of the choroid.1 The Ciliary Muscle is composed of the circular, radial, and longitudinal fibers.1 The longitudinal fibers run anterior and parallel to the sclera, and they span the majority of the Ciliary body.1,2 The circular fibers form an annulus that follows the iris, and they are connected to the longitudinal fibers via the radial fibers.1 This structural relationship allows the Muscle to act as a single functional unit.2 Early work from Woolf3 has documented the general amounts and functional ability of the Ciliary Muscle in various species (e.g., squirrels, guinea pigs, monkey); however, it was not until the early 1990s that quantitative human Ciliary Muscle measurements were documented.4 Others have since explored how Ciliary Muscle thicknesses are related to conditions like myopia,5–7 accommodation,8–10 and aging,11–13 and recently the general patterns of Ciliary Muscle development were described for the guinea pig.11 Specifically, Pucker et al.11 found with histology that guinea pig Ciliary Muscle volume increases by approximately 2.5-fold between birth (1 day) and adulthood (90 days). They also determined that Ciliary Muscle length increases by 48%, Ciliary Muscle thickness increases by 47%, and Ciliary Muscle ring diameter increases by 21% during the same time period.11 These data overall indicated that the Ciliary Muscle primarily grows via length and thickness changes more than through increases in Ciliary ring diameter.11 Currently, the processes underlying normal Ciliary Muscle growth are unknown (e.g., hypertrophy, hyperplasia, or a combination of these processes); therefore, the aim of this investigation was to characterize the cellular changes during postnatal Ciliary Muscle development. The guinea pig was chosen as the animal model to accomplish this aim because guinea pigs reach adulthood relatively quickly; guinea pigs are able to accommodate, and guinea pigs have a quantifiable amount of Ciliary Muscle that significantly increases during development,11,14,15 Regional Ciliary Muscle (nasal and temporal) differences were also studied because knowledge of regional guinea pig Ciliary Muscle differences could prove to be important for future histologic and genetic analyses.
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Anatomy and Pathology/Oncology Ciliary Muscle Cell Changes During Guinea Pig Development
2015Co-Authors: Ashley R Jackson, Hugh J Morris, Andrew J Fischer, Kirk M Mchugh, Donald O Mutti, Andrew D PuckerAbstract:PURPOSE. Guinea pig Ciliary Muscle (CM) increases robustly in volume, length, and thickness with age. We wanted to characterize CM cells during development to determine the contributions of hypertrophy (cell size increase) and hyperplasia (cell number increase) during development. METHODS. Six pigmented guinea pig eyes were collected at each of five ages: 1, 10, 20, 30, and 90 days. Refractive errors and axial lengths were determined. Eyes were temporally marked, enucleated, hemisected, and fixed. Nasal and temporal eye segments were embedded and 30-lm serial sections were collected; the two most central slides from each hemisection were analyzed with an epifluorescence microscope and Stereo Investigator software to determine normal morphologic parameters. RESULTS. Refractive errors became less hyperopic (P ¼ 0.0001) while axial lengths and CM lengths, cross-sectional areas, volumes, and cell sizes all increased linearly with log age (all P < 0.00001). Ciliary Muscle cell numbers increased only during the first 20 days of life (P ¼ 0.02). Nasal and temporal CM lengths (P ¼ 0.07), cross-sectional areas (P ¼ 0.18), and cell numbers (P ¼ 0.70) were not different, but CM cell sizes were initially larger temporally and became larger nasally after age 30 days. CONCLUSIONS. The mechanism of guinea pig CM cell growth during the first 90 days of life was characterized by early hyperplasia combined with hypertrophic cell growth throughout development that results in larger CM lengths, cross-sectional areas, and volumes. Nasaltemporal CM development was generally symmetric, but there was more CM hypertrophy nasally at older ages
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Guinea Pig Ciliary Muscle Development
Optometry and vision science : official publication of the American Academy of Optometry, 2014Co-Authors: Andrew D Pucker, Kirk M Mchugh, Ashley R. Carpenter, Donald O MuttiAbstract:ABSTRACTPurposeThe purpose of this study was to develop a method for quantifying guinea pig Ciliary Muscle volume (CMV) and to determine its relationship to age and ocular biometric measurements.MethodsSix albino guinea pigs’ eyes were collected at each of five ages (n = 30 eyes). Retinoscopy and ph
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quantification of age related and per diopter accommodative changes of the lens and Ciliary Muscle in the emmetropic human eye
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Kathryn Richdale, Loraine T Sinnott, Mark A. Bullimore, Donald O Mutti, Peter A Wassenaar, Petra Schmalbrock, Chiuyen Kao, Samuel Patz, Adrian GlasserAbstract:PURPOSE To calculate age-related and per diopter (D) accommodative changes in crystalline lens and Ciliary Muscle dimensions in vivo in a single cohort of emmetropic human adults ages 30 to 50 years. METHODS The right eyes of 26 emmetropic adults were examined using ultrasonography, phakometry, anterior segment optical coherence tomography, and high resolution magnetic resonance imaging. Accommodation was measured both subjectively and objectively. RESULTS In agreement with previous research, older age was linearly correlated with a thicker lens, steeper anterior lens curvature, shallower anterior chamber, and lower lens equivalent refractive index (all P < 0.01). Age was not related to Ciliary Muscle ring diameter (CMRD) or lens equatorial diameter (LED). With accommodation, lens thickness increased (+0.064 mm/D, P < 0.001), LED decreased (-0.075 mm/D, P < 0.001), CMRD decreased (-0.105 mm/D, P < 0.001), and the Ciliary Muscle thickened anteriorly (+0.013 to +0.026 mm/D, P < 0.001) and thinned posteriorly (-0.011 to -0.015, P < 0.01). The changes per diopter of accommodation in LED, CMRD, and Ciliary Muscle thickness were not related to subject age. CONCLUSIONS The per diopter Ciliary Muscle contraction is age independent, even as total accommodative amplitude declines. Quantifying normal biometric dimensions of the accommodative structures and changes with age and accommodative effort will further the development of new IOLs designed to harness Ciliary Muscle forces.
Andrew D Pucker - One of the best experts on this subject based on the ideXlab platform.
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morphological Ciliary Muscle changes associated with form deprivation induced myopia
Experimental Eye Research, 2020Co-Authors: Andrew D Pucker, Ashley R Jackson, Kirk M Mchugh, Donald O MuttiAbstract:Abstract Myopic children have larger Ciliary Muscles than non-myopic children, suggesting that the Ciliary Muscle may have an impact on or be affected by refractive error development. The guinea pig represents an attractive model organism for myopia development research. The purpose of the study was to investigate whether form deprivation-induced myopia in one or more strains of guinea pig causes thickening of the Ciliary Muscle as seen in human myopia. Thirty-nine guinea pigs were bred from in-house progenitors obtained from Cincinnati Children's Hospital (Cincinnati) and the United States Army (Strain 13). At 2–4 days of age the right eyes of animals were exposed to form deprivation for 7 days while the fellow eyes served as controls. Refractive error was determined with retinoscopy while vitreous chamber depth (VCD) and axial length (AL) were determined with A-scan ultrasound. Ciliary Muscle characteristics (Ciliary Muscle length, cross-sectional area, volume, cell number, cell size, and smooth Muscle actin concentration) were determined histologically with antibody labeling and analyzed according to whether the animal developed axial myopia (anisometropia > −2.00 D with VCD and/or AL differences > 0.1 mm) or was unresponsive. This analysis method yielded four groups with Group 1 having no induced myopia but with axial elongation (n = 11), Group 2 having myopia without vitreous or axial elongation (n = 8), Group 3 having myopia with either vitreous or axial elongation (n = 11), and Group 4 having myopia with both vitreous and axial elongation (n = 8). There were no post-treatment inter-ocular differences between strains or for the overall group of animals for any Ciliary Muscle variable; however, a higher response group number in multivariate ordinal regression was related to having a treated compared to fellow eye that had a lower smooth Muscle actin concentration (p = 0.006), with a shorter Ciliary Muscle length (p = 0.042), and a less oblate eye shape (p = 0.010). Guinea pig Ciliary Muscle length and smooth Muscle actin concentration were significantly less in the treated eyes of axially myopic animals suggesting that 7 days of form deprivation induced Ciliary Muscle cellular atrophy or inhibited Ciliary Muscle growth. Form deprivation myopia in the guinea pig does not result in the increase in Ciliary Muscle thickness associated with human juvenile and adult myopia.
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Ciliary Muscle cell changes during guinea pig development
Investigative Ophthalmology & Visual Science, 2015Co-Authors: Andrew D Pucker, Ashley R Jackson, Hugh J Morris, Andrew J Fischer, Kirk M Mchugh, Donald O MuttiAbstract:The Ciliary body is an important ocular structure because it produces aqueous humor, controls aqueous humor drainage (uveoscleral outflow), and produces accommodation.1 The ability to accommodate (changing the eye's refractive focus) results from flexure of the Ciliary Muscle within the Ciliary body.1 The Ciliary Muscle runs parallel to the sclera, and its anterior attachment is to the scleral spur/trabecular meshwork while its posterior attachment is to the stroma of the choroid.1 The Ciliary Muscle is composed of the circular, radial, and longitudinal fibers.1 The longitudinal fibers run anterior and parallel to the sclera, and they span the majority of the Ciliary body.1,2 The circular fibers form an annulus that follows the iris, and they are connected to the longitudinal fibers via the radial fibers.1 This structural relationship allows the Muscle to act as a single functional unit.2 Early work from Woolf3 has documented the general amounts and functional ability of the Ciliary Muscle in various species (e.g., squirrels, guinea pigs, monkey); however, it was not until the early 1990s that quantitative human Ciliary Muscle measurements were documented.4 Others have since explored how Ciliary Muscle thicknesses are related to conditions like myopia,5–7 accommodation,8–10 and aging,11–13 and recently the general patterns of Ciliary Muscle development were described for the guinea pig.11 Specifically, Pucker et al.11 found with histology that guinea pig Ciliary Muscle volume increases by approximately 2.5-fold between birth (1 day) and adulthood (90 days). They also determined that Ciliary Muscle length increases by 48%, Ciliary Muscle thickness increases by 47%, and Ciliary Muscle ring diameter increases by 21% during the same time period.11 These data overall indicated that the Ciliary Muscle primarily grows via length and thickness changes more than through increases in Ciliary ring diameter.11 Currently, the processes underlying normal Ciliary Muscle growth are unknown (e.g., hypertrophy, hyperplasia, or a combination of these processes); therefore, the aim of this investigation was to characterize the cellular changes during postnatal Ciliary Muscle development. The guinea pig was chosen as the animal model to accomplish this aim because guinea pigs reach adulthood relatively quickly; guinea pigs are able to accommodate, and guinea pigs have a quantifiable amount of Ciliary Muscle that significantly increases during development,11,14,15 Regional Ciliary Muscle (nasal and temporal) differences were also studied because knowledge of regional guinea pig Ciliary Muscle differences could prove to be important for future histologic and genetic analyses.
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Anatomy and Pathology/Oncology Ciliary Muscle Cell Changes During Guinea Pig Development
2015Co-Authors: Ashley R Jackson, Hugh J Morris, Andrew J Fischer, Kirk M Mchugh, Donald O Mutti, Andrew D PuckerAbstract:PURPOSE. Guinea pig Ciliary Muscle (CM) increases robustly in volume, length, and thickness with age. We wanted to characterize CM cells during development to determine the contributions of hypertrophy (cell size increase) and hyperplasia (cell number increase) during development. METHODS. Six pigmented guinea pig eyes were collected at each of five ages: 1, 10, 20, 30, and 90 days. Refractive errors and axial lengths were determined. Eyes were temporally marked, enucleated, hemisected, and fixed. Nasal and temporal eye segments were embedded and 30-lm serial sections were collected; the two most central slides from each hemisection were analyzed with an epifluorescence microscope and Stereo Investigator software to determine normal morphologic parameters. RESULTS. Refractive errors became less hyperopic (P ¼ 0.0001) while axial lengths and CM lengths, cross-sectional areas, volumes, and cell sizes all increased linearly with log age (all P < 0.00001). Ciliary Muscle cell numbers increased only during the first 20 days of life (P ¼ 0.02). Nasal and temporal CM lengths (P ¼ 0.07), cross-sectional areas (P ¼ 0.18), and cell numbers (P ¼ 0.70) were not different, but CM cell sizes were initially larger temporally and became larger nasally after age 30 days. CONCLUSIONS. The mechanism of guinea pig CM cell growth during the first 90 days of life was characterized by early hyperplasia combined with hypertrophic cell growth throughout development that results in larger CM lengths, cross-sectional areas, and volumes. Nasaltemporal CM development was generally symmetric, but there was more CM hypertrophy nasally at older ages
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Guinea Pig Ciliary Muscle Development
Optometry and vision science : official publication of the American Academy of Optometry, 2014Co-Authors: Andrew D Pucker, Kirk M Mchugh, Ashley R. Carpenter, Donald O MuttiAbstract:ABSTRACTPurposeThe purpose of this study was to develop a method for quantifying guinea pig Ciliary Muscle volume (CMV) and to determine its relationship to age and ocular biometric measurements.MethodsSix albino guinea pigs’ eyes were collected at each of five ages (n = 30 eyes). Retinoscopy and ph
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region specific relationships between refractive error and Ciliary Muscle thickness in children
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Andrew D Pucker, Loraine T Sinnott, Melissa D BaileyAbstract:PURPOSE: To determine if there is a relationship between refractive error and Ciliary Muscle thickness in different Muscle regions. METHODS: An anterior segment optical coherence tomographer was used to measure cycloplegic Ciliary Muscle thicknesses at 1 mm (CMT1), 2 mm (CMT2), and 3 mm (CMT3) posterior to the scleral spur; maximum (CMTMAX) thickness was also assessed. An autorefractor was used to determine cycloplegic spherical equivalent refractive error (SPHEQ). Apical Ciliary Muscle fibers were obtained by subtracting corresponding CMT2 values from CMT1 and CMTMAX. Multilevel regression models were used to determine the relationship between Ciliary Muscle thickness in various regions of the Muscle and refractive error. RESULTS: Subjects included 269 children with a mean age of 8.71 ± 1.51 years and a mean refractive error of +0.41 ± 1.29 diopters. In linear models with Ciliary Muscle thicknesses and SPHEQ, SPHEQ was significantly associated only with CMT2 (β = -11.34, P = 0.0008) and CMT 3 (β = -6.97, P = 0.007). When corresponding values of CMT2 were subtracted from CMT1 and CMTMAX, apical fibers at CMT1 (β = 14.75, P < 0.0001) and CMTMAX (β = 18.16, P < 0.0001) had a significant relationship with SPHEQ. CONCLUSIONS: These data indicated that in children the posterior Ciliary Muscle fibers are thicker in myopia (CMT2 and CMT3), but paradoxically, the apical Ciliary Muscle fibers are thicker in hyperopia (CMTMAX and CMT1). This may be the first evidence that hyperopia is associated with a thicker apical Ciliary Muscle region.
Michael Wiederholt - One of the best experts on this subject based on the ideXlab platform.
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the regulation of trabecular meshwork and Ciliary Muscle contractility
Progress in Retinal and Eye Research, 2000Co-Authors: Michael Wiederholt, Hagen Thieme, Friederike StumpffAbstract:Abstract Current models of aqueous humor outflow no longer treat trabecular meshwork (TM) as an inert tissue passively distended by the Ciliary Muscle (CM). Instead, ample evidence supports the theory that trabecular meshwork possesses smooth Muscle-like properties and is actively involved in the regulation of aqueous humor outflow and intraocular pressure. In this model, trabecular meshwork and Ciliary Muscle appear as functional antagonists, with Ciliary Muscle contraction leading to a distension of trabecular meshwork with subsequent reduction in outflow, and with trabecular meshwork contraction leading to the opposite effect. Smooth-Muscle relaxing substances would therefore appear to be ideal candidates for glaucoma therapy with the dual goal of reducing intraocular pressure via the trabecular meshwork and of improving vascular perfusion of the optic nerve head. However, for such substances to effectively lower intraocular pressure, the effect on the Ciliary Muscle would have to be minimal. For this reason, more information is needed on the signalling processes involved in regulating trabecular meshwork and Ciliary Muscle contractility. This review attempts to outline current knowledge of signal transduction pathways leading to relaxation and contraction of Ciliary Muscle and trabecular meshwork. Pathways can be classified as involving or not involving changes of membrane voltage and of requiring or not requiring external calcium; possibly, other pathways exist. These different pathways involve different ion channels and isoforms of PKC and are expressed to a differing degree in Ciliary Muscle and trabecular meshwork, leading to differential responses when exposed to relaxing or contracting pharmacological agents. Some of these agents, like tyrosine kinase inhibitors and inhibitors of PKC, have been shown to relax trabecular meshwork while leaving Ciliary Muscle comparatively unaffected. This profile makes these substances appear as ideal drugs for simultaneously improving ocular outflow and retinal circulation, parameters that determine the time course of visual deterioration in glaucoma.
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the regulation of trabecular meshwork and Ciliary Muscle contractility
Progress in Retinal and Eye Research, 2000Co-Authors: Michael Wiederholt, Hagen Thieme, Friederike StumpffAbstract:Current models of aqueous humor outflow no longer treat trabecular meshwork (TM) as an inert tissue passively distended by the Ciliary Muscle (CM). Instead, ample evidence supports the theory that trabecular meshwork possess smooth Muscle-like properties and is actively involved in the regulation of aqueous humor outflow and intraocular pressure. In this model, trabecular meshwork and Ciliary Muscle appear as functional antagonists, with Ciliary Muscle contraction leading to a distension of trabecular meshwork with subsequent reduction in outflow. and with trabecular meshwork contraction leading to the opposite effect. Smooth-Muscle relaxing substances would therefore appear to be ideal candidates for glaucoma therapy with the dual goal of reducing intraocular pressure via the trabecular meshwork and of improving vascular perfusion of the optic nerve head. However, for such substances to effectively lower intraocular pressure, the effect on the Ciliary Muscle would have to he minimal. For this reason, more information is needed on the signalling processes involved in regulating trabecular meshwork and Ciliary Muscle contractility. This review attempts to outline current knowledge of signal transduction pathways leading to relaxation and contraction of Ciliary Muscle and trabecular meshwork. Pathways can be classified as involving or not involving changes of membrane voltage and of requiring or not requiring external calcium: possibly, other pathways exist. These different pathways involve different ion channels and isoforms of PKC and are expressed to a differing degree in Ciliary Muscle and trabecular meshwork, leading to differential responses when exposed to relaxing or contracting pharmacological agents. Some of these agents. like tyrosine kinase inhibitors and inhibitors of PKC. have been shown to relax trabecular meshwork while leaving Ciliary Muscle comparatively unaffected. This profile makes these substances appear as ideal drugs for simultaneously improving ocular outflow and retinal circulation, parameters that determine the time course of visual deterioration in glaucoma.
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Direct involvement of trabecular meshwork in the regulation of aqueous humor outflow.
Current Opinion in Ophthalmology, 1998Co-Authors: Michael WiederholtAbstract:Our new hypothesis for the regulation of aqueous humor outflow suggests that the trabecular meshwork is not a passive filter but an active contractile element contributing to the Ciliary Muscle traction affecting it. The trabecular meshwork contains contractile smooth-Muscle-specific alpha-actin filaments, and its cells exhibit electrical properties typical for smooth Muscle cells. Contractility measurements performed for the first time in isolated trabecular meshwork enable a functional comparison with Ciliary Muscle. Pharmacologic outflow regulation has been determined in isolated perfused anterior segments with intact trabecular meshwork and total absence of Ciliary Muscle. Substances that contracted isolated trabecular meshwork (e.g., pilocarpine) decreased the outflow rate, whereas relaxants (e.g., low-dose epinephrine) increased it. The concept of a functional antagonism between the trabecular meshwork and the Ciliary Muscle has to be considered.
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relaxation of trabecular meshwork and Ciliary Muscle by release of nitric oxide
Investigative Ophthalmology & Visual Science, 1994Co-Authors: Michael Wiederholt, A Sturm, A LepplewienhuesAbstract:Purpose Recent evidence suggests that nitric oxide (NO) is a major messenger molecule regulating smooth Muscle contractility. A role for NO in aqueous humor dynamics, and thus regulation of intraocular pressure, has been postulated. Recently, we described contractile properties of isolated bovine trabecular meshwork and Ciliary Muscle strips. To assess whether vasodilators contribute to the regulation of trabecular meshwork and Ciliary Muscle contractility, we measured the effect of various substances known to induce vasodilation by increasing intracellular cGMP production. Methods Measurements of isometric tension were performed on isolated bovine Ciliary Muscle and trabecular meshwork strips using a custom-built electromagnetic force-length transducer. The effects of a membrane-permeable cGMP and an inhibitor of nitric oxide formation (L-nitroarginine = L-NAG) were investigated. Organic nitrate (isosorbide dinitrate = ISDN, isosorbide-5-mononitrate = 5-ISMN) and non-nitrate (sodium nitroprusside = SNP, S-nitroso-N-acetyl penicillamine = SNAP) vasodilators were tested. Results Isolated strips were precontracted by carbachol 10(-6) mol/l for 30 minutes (100% carbachol maximal contraction). 8-bromo-cGMP 10(-4) mol/l evoked a relaxation to 86.7% +/- 1.4% (n = 8) in Ciliary Muscle and 58.6% +/- 5.4% (n = 7) in trabecular meshwork. Inhibition of NO-synthase by L-NAG increased the carbachol-induced contraction. The organic nitrovasodilators ISDN and 5-ISMN produced significant relaxations. The non-nitrates SNP and SNAP were the most potent relaxants. SNP 10(-4) mol/l relaxed the isolated Ciliary Muscle to 55.5% +/- 3.5% and the trabecular meshwork to 38.6% +/- 3.6%. ISDN and SNP were also tested on isolated strips without carbachol-induced precontraction. Both vasodilators had significant relaxing activity under these conditions. Conclusion The data indicate that an increase of intracellular cGMP by application of cGMP and organic nitrate or non-nitrate vasodilators induces relaxation of the bovine trabecular meshwork and Ciliary Muscle. Thus, nitric oxide is a cotransmitter of smooth Muscle relaxation in the chamber angle and may be involved in the regulation of aqueous humor dynamics.
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differential smooth Muscle like contractile properties of trabecular meshwork and Ciliary Muscle
Experimental Eye Research, 1991Co-Authors: A Lepplewienhues, Frank Stahl, Michael WiederholtAbstract:Abstract The contractile properties of bovine trabecular meshwork and Ciliary Muscle strips were investigated using an electromagnetic force-length transducer for isometric force measurements. Acetylcholine, pilocarpine and aceclidine administration resulted in dose-dependent contractions of trabecular meshwork and Ciliary Muscle. Absolute forces were approximately 10 times larger in Ciliary Muscle than in trabecular meshwork. Maximal force evoked by aceclidine (5 × 10−5 m ), when compared to the pilocarpine (5 × 10−5 m ) response, was significantly higher in trabecular meshwork than in Ciliary Muscle. The results were 172·5 ± 12·6% (n = 7) and 138·9±4·0% (n = 8, P m ), when compared to the acetylcholine response (10−3 m ), resulted in a small contraction of 19·3±4·2% in trabecular meshwork (n = 5), and of 59·0±13·7% in Ciliary Muscle (n = 4, P m ). The differential potassium effect may be explained by the large number of cholinergic nerve endings in Ciliary Muscle as compared to trabecular meshwork tissue. Recently, a dissociation between the effects of aceclidine on outflow resistance and accommodation has been described. Our data are consistent with these observations and provide evidence for a direct role of trabecular meshwork contractility in aqueous outflow regulation.
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age related posterior Ciliary Muscle restriction a link between trabecular meshwork and optic nerve head pathophysiology
Experimental Eye Research, 2017Co-Authors: Mary Ann Croft, Elke Lutjendrecoll, Paul L KaufmanAbstract:Abstract The Ciliary Muscle plays a major role in controlling both accommodation and outflow facility in primates. The Ciliary Muscle and the choroid functionally form an elastic network that extends from the trabecular meshwork all the way to the back of the eye and ultimately attaches to the elastic fiber ring that surrounds the optic nerve and to the lamina cribrosa through which the nerve passes. The Ciliary Muscle governs the accommodative movement of the elastic network. With age Ciliary Muscle mobility is restricted by progressively inelastic posterior attachments and the posterior restriction makes the contraction progressively isometric; placing increased tension on the optic nerve region. In addition, outflow facility also declines with age and limbal corneoscleral contour bows inward. Age-related loss in Muscle movement and altered limbal corneoscleral contour could both compromise the basal function of the trabecular meshwork. Further, recent studies in non-human primates show that the central vitreous moves posteriorly all the way back to the optic nerve region, suggesting a fluid current and a pressure gradient toward the optic nerve. Thus, there may be pressure and tension spikes on the optic nerve region during accommodation and these pressure and tension spikes may increase with age. This constellation of events could be relevant to glaucomatous optic neuropathy. In summary, our hypothesis is that glaucoma and presbyopia may be literally linked to each other, via the choroid, and that damage to the optic nerve may be inflicted by accommodative intraocular pressure and choroidal tension “spikes”, which may increase with age.
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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
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Darryl R Overby, Jacques Bertrand, Martin Schicht, Friedrich Paulsen, Daniel W Stamer, Elke LutjendrecollAbstract:Purpose. To determine the connections between the Ciliary Muscle (CM), trabecular meshwork (TM), and Schlemm's canal (SC) and their innervations that allows CM contraction (by pilocarpine) to influence conventional outflow in mice.
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morphologic indication for proprioception in the human Ciliary Muscle
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Cassandra Flugelkoch, Paul L Kaufman, Winfried Neuhuber, Elke LutjendrecollAbstract:The complex process of accommodation in primates is mediated by the Ciliary Muscle that, by configurational changes of its three portions, moves anterior inwardly, thereby influencing the tension of the zonular fibers and thus the shape of the lens. This complicated process is reflected in the structure of the Ciliary Muscle itself. Unlike smooth Muscle seen in vessels or gut wall, the Ciliary Muscle has tendons for anterior and posterior attachment and the Muscle cells exhibit a regular array of dense bands and dense bodies resembling Z-stripes1,2 and histochemical staining qualities, similar to striated Muscle.3 The innervation of the Ciliary Muscle also differs from that of vessel or gut wall smooth Muscle. Ciliary Muscle cells are extremely densely innervated by cholinergic parasympathetic terminals of the oculomotor nerve1,4–6 and lack gap junctions.2,7–9 Additionally, there are large numbers of intrinsic nerve cells staining for NADPH diaphorase and nitric oxide synthase (NOS).10 These cells are present only in those primate species with a well-developed fovea centralis.11 In human eyes approximately 900 such cells are found in total, localized only in the inner circular and reticular portions of the Ciliary Muscle, where they are assumed to induce relaxation of the Muscle cells.10 In contrast to this prominent efferent innervation, sparse data exist about the Muscle's afferent neurons. Large nerve endings are present in the scleral spur of human eyes, where the tendons of the outer longitudinal Ciliary Muscle portion insert.12,13 Also within the trabecular meshwork, where tendons of the Ciliary Muscle radiate to form connections between the Muscle and the aqueous humor outflow region, afferent terminals staining for calcitonin gene-related peptide (CGRP) and substance P (SP) are often found in contact with elastic fibers.13 Similar results have also been obtained for the monkey eye.14 Morphologically, these nerve endings resemble the afferent terminals of visceral mechanoreceptors measuring stretch or distension. The presence of afferent nerve endings perceiving tension or shearing forces in smooth Muscle is not unusual. In the gastrointestinal tract, abundant endings have been located in the connective tissue between the two Muscle layers of the muscular wall (for reviews see Refs. 15–17). In other tissues such as vasculature (for reviews see Refs. 18–20), periodontal tissue (for reviews see Refs. 21, 22), urogenital,23,24 and respiratory tract (for reviews see Refs. 25–28), afferent endings representing proprioreceptors have been described. In most cases the putative muscular mechanoreceptors express the calcium-binding proteins calretinin and calbindin.16,29–34 Within the vagal mechanosensory terminals in the tunica muscularis of the esophagus (the intraganglionic laminar endings) and in vagal bronchopulmonary and skeletomuscular mechanosensors, the presence of vesicular glutamate transporter 2 (VGLUT 2) has been detected.16 The complex process of Ciliary Muscle contraction and its significance for dynamic, precise, and rapid visual focus on objects at any distance suggests the existence of afferent proprioreception to modulate the rapid and controlled adjustment of the fine Muscle movements needed for efficient accommodation and disaccommodation. In the present study, we have, therefore, examined the entire human Ciliary Muscle and its posterior and anterior tendons with respect to proprioreceptive nerve endings using immunohistochemical staining methods applied to sections cut in different planes and to various wholemount preparations. Additionally, selected specimens fixed in glutaraldehyde were investigated ultrastructurally.
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aqueous humor dynamics and trabecular meshwork and anterior Ciliary Muscle morphologic changes with age in rhesus monkeys
Investigative Ophthalmology & Visual Science, 2003Co-Authors: B'ann T. Gabelt, Paul L Kaufman, Elke Lutjendrecoll, Johannes GottankaAbstract:PURPOSE. To determine in rhesus monkeys the age-dependence of uveoscleral outflow (Fu) and morphology of the trabecular meshwork (TM) and anterior Ciliary Muscle (CM). METHODS. Intraocular pressure (IOP) was measured by Goldmann applanation tonometry in monkeys under ketamine anesthesia. After anterior chamber cannulation under pentobarbital anesthesia, aqueous humor formation (AHF), anterior chamber volume, trabecular outflow, and Fu were determined isotopically. The CM and TM were examined by light and electron microscopy. RESULTS. IOP increased significantly with age in monkeys aged 3 to 29 years. AHF and anterior chamber volume were unchanged. Fu was decreased, and trabecular outflow increased in monkeys aged 25 to 29 years compared with the remaining monkeys. Morphologically, there was a significant increase in the thickness of the elastic fibers of the trabeculum ciliare covering the anterior tips of the CM, and an increase in extracellular material between the Muscle tips. The number of TM cells decreased with age, whereas the amount of fibrillar material and sheath-derived plaques increased. This increase was less pronounced in the middle filtering portion of the cribriform region than in the anterior and posterior portions. CONCLUSIONS. The decline in Fu in very old rhesus monkeys with normal IOP parallels that seen in normotensive aging humans. This may be correlated with thickening of the elastic fiber sheath in the CM tips in addition to other morphologic changes. The TM findings are analogous to those in the aging human eye and are consistent with the age-related decrease in outflow facility reported in both humans and monkeys. (Invest Ophthalmol Vis Sci. 2003;44:2118 ‐2125) DOI:10.1167/ iovs.02-0569 I
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age related loss of Ciliary Muscle mobility in the rhesus monkey role of the choroid
Archives of Ophthalmology, 1992Co-Authors: Ernst R. Tamm, Mary Ann Croft, Elke Lutjendrecoll, Wilfried Jungkunz, Paul L KaufmanAbstract:• Ciliary Muscle topography was studied in rhesus monkey eyes (aged 6 to 29 years) bisected meridionally through cornea and optic nerve head. Half of each eye was incubated in atropine sulfate, the other in pilocarpine hydrochloride, and both were then processed for histologic study. Several Ciliary Muscle sections from the original cut margin and the middle of the half eyes were traced and compared quantitatively. In sections from the middle, where the attachments of the Muscle were presumably intact, the pilocarpine effect on Ciliary Muscle topography was lost with age. In sections near the cut margin, where some of the posterior attachments were disrupted and the choroid had detached from the sclera, the pilocarpine effect persisted with age. These findings suggest that loss of Ciliary Muscle movement with age is caused by decreased compliance of its posterior attachment.