purpose. To study the effects of 2-arachidonyl glyceryl ether (noladin ether), an endocannabinoid ligand selective for cannabinoid (CB)1 receptor, on aqueous humor outflow facility, to investigate the involvement of trabecular meshwork CB1 receptors and the p42/44 MAP kinase signaling pathway and to explore the cellular mechanisms of noladin ether-induced changes of outflow facility.. methods. The effects of noladin ether on aqueous humor outflow facility were measured in a porcine anterior-segment-perfused organ culture model. The expression of CB1 receptors on cultured porcine trabecular meshwork cells and the coupling of these receptors to p42/44 MAP kinase was determined by immunofluorescence microscopy and Western blot analysis. Both Western blot and zymography were used to monitor the effects of noladin ether on matrix metalloproteinase (MMP)-2. In morphologic studies, AlexaFluor 488-labeled phalloidin staining was used to examine actin filament, and immunohistochemistry with anti-paxillin ...
Our analyses indicate that PITX2 activates genes in the anterior segment of the eye involved in a variety of key processes, including response to cellular stress. Cellular stress can be induced by the generation of reactive oxygen species (ROS), and many experimental studies have shown that local oxidative stress induced by ROS is a determining factor in the pathology of glaucoma. In vitro studies have shown that TM cell morphology is altered on exposure to hydrogen peroxide by compromising cellular integrity and cell adhesion. 14 In addition, aqueous humor drainage from the anterior chamber of the calf eye is affected when TM cells are perfused with hydrogen peroxide. 15 Moreover, it has been shown in humans that TM cells from glaucoma patients presented more oxidative DNA damage than unaffected controls, and this damage is significantly correlated with the elevation of IOP and visual field damage. 13,16 Our studies indicate that reduction in PITX2 protein levels produced an increase in ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
TY - JOUR. T1 - Effects of lentivirus-mediated C3 expression on trabecular meshwork cells and intraocular pressure. AU - Tan, Junkai. AU - Fan, Ning. AU - Wang, Ningli. AU - Feng, Bingkai. AU - Yang, Ming. AU - Liu, Guo. AU - Wang, Yun. AU - Zhu, Xianjun. AU - Kaufman, Paul L.. AU - Pang, Iok Hou. AU - Liu, Xuyang. PY - 2018/10. Y1 - 2018/10. N2 - PURPOSE. We evaluated the effects of lentivirus-mediated exoenzyme C3 transferase (C3) expression on cultured primary human trabecular meshwork (HTM) cells in vitro, and on rat intraocular pressure (IOP). METHODS. HTM cells were cultured and treated with lentivirus vectors expressing either green fluorescent protein (GFP) only (LV-GFP) or GFP and C3 together (LV-C3-GFP). Changes in cell morphology and actin stress fibers were assessed. The vectors were also injected into the anterior chamber of rats, and GFP expression was visualized by a Micron III Retinal Imaging Microscope in vivo and a fluorescence microscope ex vivo. Changes in rat IOP were ...
TY - JOUR. T1 - The effect of dexamethasone on glycosaminoglycans of human trabecular meshwork in perfusion organ culture. AU - Johnson, D. H.. AU - Bradley, J. M B. AU - Acott, Ted. PY - 1990. Y1 - 1990. N2 - The effect of dexamethasone treatment on glycosaminoglycans (GAG) in the human trabecular meshwork was studied by placing 20 pairs of eyes in perfusion organ culture. One eye received 550 nM dexamethasone in addition to culture medium; the fellow eye received culture medium only. 3H-glucosamine and 35S-sulfate were added to the medium for the final 48 hr of culture. The meshwork was then dissected, and the GAGs were isolated and subjected to sequential enzymatic degradation. Active labeling of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparan sulfate was found in both control and steroid-treated eyes. Dexamethasone-treated eyes had an average 92% increase in the 3H-glucosamine incorporation rate in the undigestible GAG residue fraction after 14-21 days ...
Exosomes are emerging as important mediators of cell-matrix interactions by means of specific adhesion proteins. Changes in the tissue-specific exosomal protein expression may underlie pathological conditions whereby extracellular matrix turnover and homeostasis is disrupted. Ocular hypertension due to extracellular matrix accumulation in the trabecular meshwork is a hallmark of glucocorticoid-induced glaucoma. In the trabecular meshwork, exosomal fibronectin mediates cell matrix interactions at cellular structures called invadosomes. Trabecular meshwork cells use invadosomes to turn over their surrounding matrix and maintain passageways for flow of aqueous humor. In this study, we observed that human trabecular meshwork explants treated with dexamethasone released exosomes with significantly reduced amounts of fibronectin bound per exosome. Further, we found that exosome-fibronectin binding is heparan sulfate-dependent, consistent with our observation that trabecular meshwork exosomes are ...
Deposition of extracellular matrix (ECM) in trabecular meshwork, such as fibronectin, collagen IV, elastin. leads to increased resistance of trabecular meshwork in primary open angle glaucoma (POAG). Connective tissue growth factor (CTGF) is known to regulate the ECM deposits. In this study, we detect the effect of adenovirus conducted CTGF (Adv-CTGF) transfection on either the expression of ECM components or aqueous humor outflow facility. Adv-CTGF was used to transfect rat trabecular meshwork cells in vivo and in vitro. Aqueous humor outflow facility was test by microbeads perfusion. Protein expression of CTGF, fibronectin, and collagen IV was determined using Western blot. In the Adv-CTGF group, the outflow facility displayed a significant decrease from baseline. It appears as though the transfection with Adv-CTGF significantly affects the aqueous humor outflow pattern. A negative correlation between IOP and PEFL indicated that a decrease in the area of bead deposition corresponded to an overall
TY - JOUR. T1 - Effects of induction and inhibition of matrix cross-linking on remodeling of the aqueous outflow resistance by ocular trabecular meshwork cells. AU - Yang, Yong Feng. AU - Sun, Ying Ying. AU - Acott, Ted. AU - Keller, Kate. PY - 2016/7/28. Y1 - 2016/7/28. N2 - The trabecular meshwork (TM) tissue controls drainage of aqueous humor from the anterior chamber of the eye primarily by regulating extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs). Glaucomatous TM tissue is stiffer than age-matched controls, which may be due to alterations in ECM cross-linking. In this study, we used genipin or beta-Aminopropionitrile (BAPN) agents to induce or inhibit matrix cross-linking, respectively, to investigate the effects on outflow resistance and ECM remodeling. Treatment with BAPN increased outflow rates in perfused human and porcine anterior segments, whereas genipin reduced outflow. Using a fluorogenic peptide assay, MMP activity was increased with BAPN treatment, but ...
Surgical methods and related medical devices for treating glaucoma are disclosed. The method comprises trabecular bypass surgery, which involve bypassing diseased trabecular meshwork with the use of a seton implant. The seton implant is used to prevent a healing process known as filling in, which has a tendency to close surgically created openings in the trabecular meshwork. The surgical method and novel implant are addressed to the trabecular meshwork, which is a major site of resistance to outflow in glaucoma. In addition to bypassing the diseased trabecular meshwork at the level of the trabecular meshwork, existing outflow pathways are also used or restored. The seton implant is positioned through the trabecular meshwork so that an inlet end of the seton implant is exposed to the anterior chamber of the eye and an outlet end is positioned into fluid collection channels at about an exterior surface of the trabecular meshwork or up to the level of aqueous veins.
Surgical methods and related medical devices for treating glaucoma are disclosed. The method comprises trabecular bypass surgery, which involve bypassing diseased trabecular meshwork with the use of a seton implant. The seton implant is used to prevent a healing process known as filling in, which has a tendency to close surgically created openings in the trabecular meshwork. The surgical method and novel implant are addressed to the trabecular meshwork, which is a major site of resistance to outflow in glaucoma. In addition to bypassing the diseased trabecular meshwork at the level of the trabecular meshwork, existing outflow pathways are also used or restored. The seton implant is positioned through the trabecular meshwork so that an inlet end of the seton implant is exposed to the anterior chamber of the eye and an outlet end is positioned into fluid collection channels at about an exterior surface of the trabecular meshwork or up to the level of aqueous veins.
Trabecular Meshwork (TM) contractile state is thought to affect aqueous humor outflow and Intraocular Pressure (IOP). It has been suggested that TM relaxation may increas..
Analysis of microarray gene expression data can be confounded by compound effects of technical parameters causing false positive and false negative identifications and by low but biologically significant differences in expression levels of some genes [47]. With these considerations in mind, we analyzed the array data using three different protocols, the commonly used protocol available in the Limma package and two additional ones that we designed [15]. The likelihood of a selected gene being a true positive was considered to correlate with the number of protocols by which it was selected. By considering all genes that were selected by at least one protocol, the likelihood of false negatives was expected to decrease. The Limma protocol is based on statistical parameters [15]. Protocols 2 and 3 are both based on fold change in expression levels, with the consideration that genes that show larger fold change are likely to be true positives [47]. Furthermore, data emanating from protocol 1 do not ...
Comments from Dr. Masaki Tanito, "These hooks are developed to perform trabeculotomy by ab interno approach under the observation of trabecular meshwork by using gonioprism. A straight type is suitable for temporal approach to the nasal meshwork or for superior approach to the inferior meshwork; angled-left and -right hooks are suitable for nasal approach to the temporal meshwork. The tip of the hook is enough sharp to enter directly into the Schlemms canal; trabecular meshwork is easily incised by moving the tip of the hook circumferentially. To avoid unintended damage to the outer wall of Schlemms canal, keeping the proper depth of the tip is critical. At the proper depth, metal reflex of the tip of the hook is visible through the meshwork tissue. Invisibility of the tip and any resistance during the incision indicate that the position of the hook is too deep; in such case, pull the tip to the meshwork surface to reappear the metal reflux through the meshwork and incise the meshwork at a ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
In our study, 2PM was used to image the trabecular drainage channels of intact enucleated rat eyes. Due to the intrinsic properties of drainage tissue, autofluorescence from collagen fibers can be used to image the microstructure of the pathway. Compared to external fluorescent label, autofluorescence can avoid tissue damage caused by fluorochrome. Meanwhile, 2PM is suited to tissue imaging under the sclera, and has been successfully used to image living skin at a depth of 350 μm by visualizing the 2PAF of the skins extracellular matrix and melanin [19]. Most importantly of all, we were able to successfully get the high resolution images under high scattering tissue of eye. Our imaging had a lateral resolution of 2 μm, and a depth resolution of 1 μm. It is found that the high resolution imaging can achieve resolution of tissue section, and can avoid tissue distortions caused by infusion of fixatives.. Aqueous humor drains into aqueous vein through TM region firstly. In this progress, TM and ...
Purpose: Glaucoma is a leading cause of irreversible blindness in the world. TGF-β2 is elevated in glaucoma eyes and is an important factor in the extracellular matrix (ECM) metabolism of human trabecular meshwork (HTM) cells, leading to increased intraocular pressure (IOP). Both LOX and TGM2 enzymes are important in cross-linking the ECM in HTM cells. As TGF-β2 up regulates LOX and TGM2 expression, the aim of this experiment is to determine and quantify the amount of LOX- and TGM2-induced ECM crosslinking in glaucomatous trabecular meshwork cells (GTM). Methods: LOX and TGM2 cDNAs were obtained and amplified by PCR with specifically designed primers and isolated by gel electrophoresis. The cDNAs were ligated into the pGEM-T plasmid vector and cloned into E. coli gold cells. After sequencing, the genes were restriction digested and ligated to a pacAd5 vector to generate adenovirus expression vectors, which have a high selectivity for TM cells. The pacAd5 vectors will be used to transduce the GTM3 cell
Take-home message: New discoveries about the signaling pathways regulating cross-linked actin network (CLAN) formation could in the future lead to new therapeutic approaches for steroid-induced glaucoma. CLANs are found in glaucomatous trabecular meshwork cells as well as steroid-treated cell and eye organ cultures, thus the discovery of two distinct signaling pathways is a preliminary step toward targeting of specific proteins associated with steroid-inducedglaucoma.
The major risk factor for most glaucomas and focus of modeling and treatment is increased intraocular pressure. Intraocular pressure is a function of production of liquid aqueous humor by the ciliary body of the eye and its drainage through the trabecular meshwork. Aqueous humor flows from the ciliary bodies into the posterior chamber, bounded posteriorly by the lens and the zonule of Zinn and anteriorly by the iris. It then flows through the pupil of the iris into the anterior chamber, bounded posteriorly by the iris and anteriorly by the cornea. From here the trabecular meshwork drains aqueous humor via Schlemms canal into scleral plexuses and general blood circulation. In open angle glaucoma there is reduced flow through the trabecular meshwork; in angle closure glaucoma, the iris is pushed forward against the trabecular meshwork, blocking fluid from escaping ...
Purpose. human TM cells morphologically and started to specific many guns of TM cells while ceasing to specific pluripotency guns such as Nanog, April4, and Sox2. Functionally, the ability was created by these cells to phagocytose particles. Finally, publicity to dexamethasone or phorbol 12-myristate acetate triggered a specific boost in the creation and release of myocilin and matrix metalloproteinase-3, respectively, behavior quality of TM cells. Results. Our data show that iPSCs can be induced to assume a phenotype that resembles native TM cells in many important aspects. Not only do these cells represent a valuable research tool, but transplantation into glaucomatous eyes with elevated IOP may also restore function to the TM, resulting in re-establishment of IOP. … In order to induce iPSCs to differentiate into TM-like cells, iPSCs were cocultured with the human cell line hTM530 for up to 21 days. This immortalized cell line was used here since it grows at a very consistent rate and ...
Moreover, these parameters undergo considerable changes in bone diseases. In particular, diseases such as osteoporosis, cause a decrease of the Tb.N and Tb.Th, and conversely an increase of the Tb.Sp value [28]. Gray levels Since it is known that a denser material has a higher attenuation coefficient of X-rays, a grey level of an image obtained by an X-ray irradiation of a specimen can be correlated with density of the material so the grey level of each voxel represents the mineral content of the trabecular bone [29]. According to this and observing the histograms reported in Figure 2A, it can be observed that a peaky distribution, which could be seen for the OP specimens OP1 and OP2 and CA specimens CA3 and CA4 indicates a high trabecular tissue density. Conversely, CA1 and CA2 specimens exhibit a broader distribution around the highest grey levels and thus a lower density of the trabecular tissue. This can also be observed in Figure 1, where slices of specimens characterized by a peaky ...
Purpose: Elevated intraocular pressure (IOP) is one of the main risk factors in the development of glaucoma. TGFβ2 is well known to be involved in regulating both the extracellular matrix in the trabecular meshwork (TM) as well as ocular hypertension. BAMBI (BMP and activin membrane-bound inhibitor) has been shown to be a negative regulator of TGF-β2. However, the role of BAMBI in regulating IOP is unknown. We investigated whether knockdown of BAMBI results in ocular hypertension in mice changes to the ECM in the TM due to uninhibited TGFβ2 signaling. Methods: B6;129S1-Bambitm1Jian/J mice were injected intravitreally with 2.5x107 pfu of either Ad5.TGFβ2 (n=10), Ad5.Cre (n=9), or Ad5.TGFβ2 + Ad5.Cre (n=10), in one eye of each animal. The contralateral uninjected eyes were used as negative controls. IOP was measured using a TonoLab rebound tonometer. BAMBI and Fibronectin expression was assessed in the TM by immunohistochemistry on cross-sections of eyes from Bambitm1Jian/J floxed mice and
A device and method are provided for improved treatment of elevated intraocular pressure due to glaucoma. A trabecular shunting device is adapted for implantation within the trabecular meshwork of an eye such that aqueous humor flows controllably from the anterior chamber of the eye to Schlemms canal, bypassing the trabecular meshwork. The trabecular shunting device may utilize a quantity of pharmaceuticals effective in treating glaucoma, which are controllably released from the device into cells of the trabecular meshwork and/or Schlemms canal. Depending upon the specific treatment contemplated, pharmaceuticals may be utilized in conjunction with the trabecular shunting device such that aqueous flow either increases or decreases as desired. Placement of the trabecular shunting device within the eye, and release of a glaucoma medication therefrom, can arrest or slow the progression of glaucoma.
Our results showed that miR-29b negatively regulates the expression in HTM cells of multiple genes involved in ECM synthesis, deposition, and remodeling. In addition, incubation under chronic oxidative stress conditions (4 days, 40% oxygen) resulted in a significant downregulation of miR-29b in two of the three HTM cell lines analyzed. This downregulation was associated with an increase in the expression of several ECM genes known to be regulated by miR-29b. The upregulation of these genes by chronic oxidative stress was inhibited by transfection with miR-29b mimic. The multiple effects on the expression of ECM components observed in HTM cells were consistent with the antifibrotic activity previously reported for miR-29b in the heart [19]. These effects include the downregulation of validated targets, such as COL1A1, COL1A2, COL3A1, FBN1, and SPARC [19,22]. MiR-29b also downregulated numerous genes that have not been confirmed as direct targets of this miRNA. Some of these genes contained ...
Primary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemms canal (SC) and the trabecular meshwork. We previously identified loss-of-function mutations in the angiopoietin (ANGPT) receptor TEK in families with PCG and showed that ANGPT/TEK signaling is essential for SC development. Here, we describe roles for the major ANGPT ligands in the development of the aqueous outflow pathway. We determined that ANGPT1 is essential for SC development, and that Angpt1-knockout mice form a severely hypomorphic canal with elevated intraocular pressure. By contrast, ANGPT2 was dispensable, although mice deficient in both Angpt1 and Angpt2 completely lacked SC, indicating that ANGPT2 compensates for the loss of ANGPT1. In addition, we identified 3 human subjects with rare ANGPT1 variants within an international cohort of 284 PCG patients. Loss of function in 2 of the 3 patient alleles was observed ...
Primary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemms canal (SC) and the trabecular meshwork. We previously identified loss-of-function mutations in the angiopoietin (ANGPT) receptor TEK in families with PCG and showed that ANGPT/TEK signaling is essential for SC development. Here, we describe roles for the major ANGPT ligands in the development of the aqueous outflow pathway. We determined that ANGPT1 is essential for SC development, and that Angpt1-knockout mice form a severely hypomorphic canal with elevated intraocular pressure. By contrast, ANGPT2 was dispensable, although mice deficient in both Angpt1 and Angpt2 completely lacked SC, indicating that ANGPT2 compensates for the loss of ANGPT1. In addition, we identified 3 human subjects with rare ANGPT1 variants within an international cohort of 284 PCG patients. Loss of function in 2 of the 3 patient alleles was observed ...
While conventional wisdom has considered Schlemms canal (also known as the scleral venous sinus) as a vein, the canal shares several structural and functional features reminiscent of the lymphatic vasculature. Notably, it is never filled with blood in physiological settings as it does not receive arterial blood circulation.[5] Three recent independent pioneering studies by Aleksanteri Aspelund and Kari Alitalo from the University of Helsinki, Dae-Young Park and Koh Gou Young from the Institute for Basic Science and KAIST, and Krishnakumar Kizhatil and Simon W. M. John from the Howard Hughes Medical Institute, discovered that Schlemms canal displays several features of lymphatic endothelium, including the expression of PROX1, VEGFR3, CCL21, FOXC2, but lacked the expression of LYVE1 and PDPN, indicating that Schlemms canal is a lymphatic-like vessel.[2][3][4] Developmental studies revealed that Schlemms canal develops via a unique mechanism involving the transdifferentiation of venous ...
Glaucoma is the main cause of irreversible blindness in the world. In most common types of the disease, the optic nerve is damaged by an increase in intraocular pressure (IOP) which blocks fluid drainage through canals in the eye. There is currently no cure, however, the disease can be treated by lowering IOP. Unfortunately, all IOP-lowering drugs that in the market today target the secondary drainage pathway which mediates only 5-15% of fluid outflow. Therefore, the main goal in glaucoma research has been to identify targets in the primary outflow pathway mediated through the trabecular meshwork tissue. David Krizajs group at the Moran Eye Institute (University of Utah School of Medicine) has done just that.. In a paper just published in Scientific Reports, they identify TRPV4, a mechanosensitive ion channel, as the main trabecular target of increased IOP. This highly collaborative project combined genetic, molecular, whole animal approaches with bioengineered nanoscaffold models of glaucoma ...
Yiqin Du, MD, PhD Assistant Professor of Ophthalmology University of Pittsburgh School of Medicine Lab Personnel Andrew E. Yang (Research Technician) Zoey Yi Zhou (Graduate Student)
GLAUCOMA Should you be targeting collector channels with MIGS? by Liz Hillman Editorial Co-Director Targeting an area with increased pigmentation and blood reflux into Schlemms canal (red line) adjacent to a blue mark on the cornea (black line) that identified a collector channel Source: Paul Harasymowycz, MD With newer stenting devices bypassing the trabecular meshwork or
Conventional treatment options include eye drops, laser therapy (especially for the narrow angle variety) and surgery, and are required if the patient continues to lose peripheral vision (tested by visual field exams).. The fluid pressure between the iris and the cornea builds up because the trabecular meshwork (the filter on the eyes drainpipe) becomes unable do its job properly. This is a bit more complex than it sounds. Recent evidence shows that there is a functional relationship between the ciliary body, which pulls, and the trabecular meshwork, which then distends and blocks fluid outflow. Originally thought to be a passive participant, it now seems that the trabecular meshwork itself has the ability to contract and open itself for fluid drainage (Wiederholt et al., 2000).. The goal of internal herbal therapy is to preserve visual function and maintain the health of the optic nerve. The ideal medicine for glaucoma should improve microcirculation to the back of the eye, nourish and ...
In glaucoma, aqueous outflow into the Schlemms canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular, system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated ...
The Kahook Dual Blade (KDB) is an single-use ophthalmic blade with a micro-engineered profile which allows for insertion into the eye through a clear cornea micro-incision. It can be done with or without cataract surgery, and when done in conjunction with cataract surgery it is done following lens removal through the same incision utilized for the cataract removal. The device is made of surgical grade stainless steel body with a long, thin shaft that allows for access across the anterior chamber to the trabecular meshwork (TM). Using a special mirrored lens, the surgeon uses the Kahook Dual blade to make parallel incisions in the trabecular meshwork (TM), un-roofing it and opening up into inner wall of the Canal of Schlemm to improve aqueous humor outflow from the eye in an effort to reduce the eye pressure. This procedure does not involve opening up the conjunctival tissues; this is a major advantage of this procedure as it makes future glaucoma surgery (if needed) a lot simpler with less risk ...
Several studies have used glucocorticoid-induction of myocilin as a model system of functional changes associated with POAG. One study looked at changes in the trabecular meshwork in a bovine model of prednisolone-induced IOP increases.18 The researchers documented accumulation of extracellular matrix plaques at the TM outflow loops and an increase in the TM basement membrane. In an earlier study, investigators examined expression of normal and mutant forms of myocilin;19 they showed that the wild-type protein is expressed in many different tissues; in the TM its resident in the intracellular endoplasmic reticulum and is also secreted into the aqueous humor. In cultured TM cells or cell lines, most mutant forms of myocilin accumulated in the ER and were not secreted; when mutant and native forms were co-expressed, the mutants exerted a dominant-negative effect preventing secretion of the wild type.20 Still other mutations displayed a preferential expression and secretion over the wild-type gene ...
ធម្មតា ការផលិតទឹកក្នុងភ្នែករបស់យើង (Aqueous humour) ចាប់ផ្តើមចេញពីគល់ប្រស្រីភ្នែក (Ciliary body) ដែលជាកន្លែងផលិត បន្ទាប់មកវាហូរមកបន្ទប់ផ្នែកខាងក្រោយ រួចបន្តមកបន្ទប់ភ្នែកខាងមុខ ហើយត្រូវបានស្រូបចេញតាមចម្រោះ Trabecular Meshwork និងបន្តចេញមកតាម បំពង់តូច (Schlemms canal) ហើយចុងបញ្ចប់ជ្រាបតាមសរសៃវ៉ែន (Episcleral vein) ...
有了眼睛成像的大致概念後,接下來就來詳細介紹肉眼觀察不到的部份,也就是眼睛裡所深藏的秘密。. 1. Sclera【鞏膜】 :鞏膜即一般人所稱「眼白」的部份,為眼球壁最外一層,堅韌而不透明。鞏膜可保護眼球內部,並維持眼球的形狀。. 2. Trabecular meshwork【小粱網】 :小梁網負責大部份的房水外流,受傷的小梁網組織結構導致房水引流受阻、眼壓升高,造成青光眼的發生。(房水:又譯水狀液,是充滿眼球前房和後房的透明液體,由睫狀體的無色素上皮細胞分泌。房水向眼內的一些無血管的組織提供營養,例如晶狀體和角膜內皮。房水的生成和排出的動態平衡是維持眼壓的重要方式,大部分治療青光眼的藥物通過控制房水的生成或者排出來降低眼壓。). 3. Schlemms canal(Scleral venous sinus)【許萊姆氏管】 ...
The ability to predict the mechanical properties of cells should be seen in the light of the close connection between abnormal cell states and a change in the cell response to stimuli. For example, it has been found that the stiffness of cancer cells is much lower than their healthy counterparts, influencing metastasis and cell migration. On the contrary, malaria cells have been found to exhibit a significant increase in stiffness.. The major structural entity of the cell is called the cytoskeleton, an interior network consisting of three types of protein filaments - actin filaments, intermediate filaments and microtubules. The remodelling ability of the cytoskeleton through polymerisation provides the cell with the ability to adapt its response to external forces accordingly. The properties of interfilament cross-links in terms of stiffness and ability to detach can be expected to influence the mechanical response. The work presented herein focuses on the mechanical response of cross-linked ...
Kim, T., Hwang, W., and Kamm, R.D. (2009). Computational analysis of a cross-linked actin network. Experimental Mechanics, 49, 91-104. PMID: 23601624.. Kim, T., Hwang, W., Lee, H., and Kamm, R.D. (2009). Computational analysis of viscoelastic properties of crosslinked actin networks. PLoS Computational Biology, 5(7), e1000439. PMCID: PMC2703781.. Kim, T., Hwang, W., and Kamm, R.D. (2011). Dynamic role of cross-linking proteins in actin rheology. Biophysical Journal, 101(7), 1597-1603. PMCID: PMC3183755.. Borau, C.*, Kim, T.*, Bidone, T., García-Aznar J.M., and Kamm, R.D. (2012). Dynamic mechanisms of cell rigidity sensing: insights from a computational model of actomyosin networks. PLoS One, 7(11), e49174. PMCID: PMC3489786.. Kim, T., Gardel, M.L., and Munro, E. (2014). Determinants of fluidlike behavior and effective viscosity in cross-linked actin networks. Biophysical Journal, 106(3), 526-534. PMCID: PMC3944977.. Bidone, T.C., Kim, T., Deriu, M.A., Morbiducci, U., and Kamm, R.D. (2015) ...
The mechanical properties of a cell are defined mainly by the cytoskeleton. One contributor within this three-dimensional structure is the actin cortex which is located underneath the lipid bilayer. It forms a nearly isotropic and densely cross-linked protein network. We present a continuum mechanical formulation for describing the mechanical properties of in vitro model systems based on their micro-structure, i.e. the behavior of a single filament and its spatial arrangement. The network is considered elastic, viscous effects being neglected. Filamentous actin is a biopolymer with a highly nonlinear force-stretch relationship. This can be well described by a worm-like chain model that includes extensibility of the filament, which we call the . β-model. A comparison with experimental data shows good agreement with values for the physically interpretable parameters. To make these properties applicable to three dimensions we used a non-affine micro-sphere network, which accounts for filaments, ...
Glaucoma is most commonly caused by a raised pressure in the eye (intraocular pressure). The eye is like a balloon where some fluid (aqueous humor) is getting produced by the ciliary processes and entering the eye and some fluid is exiting through a sieve like structure called the trabecular meshwork. If the outflow is obstructed then slowly the fluid builds up inside the eye and pressure rises. Most of the times medications can help reduce the pressure by either reducing fluid production or increasing outflow but sometimes when this is not enough to lower the eye pressure, a surgery needs to be done. The surgery is called a trabeculectomy or filtering surgery. In this procedure, a small part of the trabecular meshwork is cut and removed creating a hole (ostium) which allows the fluid accumulated in the eye to exit out into the space outside the globe but below the conjunctiva. This is done in a controlled manner by creating a flap of tissue (scleral flap) which keeps the ostium covered and ...
Glaucoma is most commonly caused by a raised pressure in the eye (intraocular pressure). The eye is like a balloon where some fluid (aqueous humor) is getting produced by the ciliary processes and entering the eye and some fluid is exiting through a sieve like structure called the trabecular meshwork. If the outflow is obstructed then slowly the fluid builds up inside the eye and pressure rises. Most of the times medications can help reduce the pressure by either reducing fluid production or increasing outflow but sometimes when this is not enough to lower the eye pressure, a surgery needs to be done. The surgery is called a trabeculectomy or filtering surgery. In this procedure, a small part of the trabecular meshwork is cut and removed creating a hole (ostium) which allows the fluid accumulated in the eye to exit out into the space outside the globe but below the conjunctiva. This is done in a controlled manner by creating a flap of tissue (scleral flap) which keeps the ostium covered and ...
History and purpose: Trabecular meshwork (TM) can be an ocular cells mixed up in rules of aqueous humour outflow and intraocular pressure (IOP). and mobilization of intracellular Ca2+ shops. A PTX-sensitive upsurge in extracellular signal-regulated kinase (ERK1/2) phosphorylation was also seen in response to WIN55 212 indicative of the Gi/o signalling pathway. CB1-Gq/11 coupling to activate PLC-dependent raises in Ca2+ were particular to WIN55 212 and werent observed with additional.. Read More. ...
In this study we examined the function(s) of syndecan-4 in regulating the forming of an Axitinib actin geodesic dome structure called a cross-linked actin network (CLAN) where syndecan-4 has previously been localized. and a laminin 5-produced syndecan-4-binding peptide (PEP75) induces CLAN development in TM Axitinib cells. This PEP75-induced CLAN development was inhibited by heparin as well as the wide range PKC inhibitor Ro-31-7549. On the other hand the more particular PKCα inhibitor Move 6976 acquired no effect hence excluding PKCα being a downstream effector of syndecan-4 signaling. Evaluation of PKC isozyme appearance demonstrated that HTM cells also portrayed both PKCγ and PKCε. Cells treated with a PKCε agonist created CLANs while a PKCα/γ agonist experienced no effect. These data suggest that syndecan-4 is essential for CLAN formation in HTM cells and IL-7 that a novel PKCε-mediated signaling pathway can regulate formation of this exclusive actin structure. development of ...
Devices, methods and kits are described for reducing intraocular pressure. The devices include a support that is implantable within Schlemms canal and that may restore or maintain at least partial patency of the canal without substantially interfering with transmural or transluminal fluid flow across the canal. The devices utilize the natural drainage process of the eye and may be implanted with minimal trauma to the eye. Kits may include a support and an introducer for implanting the support within Schlemms canal. Methods may include implanting a support within Schlemms canal, where the support is capable of restoring or maintaining at least partial patency of the canal without substantial interference with transmural or transluminal fluid flow across the canal.
Cause contraction of the ciliary muscle which pulls the scleral spur to tighten the trabecular meshwork, increasing the outflow of aqueous ...
A glucocorticoid-induced protein, TIGR, that is produced by cells of the trabecular meshwork can be used to diagnose glaucoma. The TIGR protein, anti-TIGR antibodies, and TIGR encoding sequences also provide a diagnostic for glaucoma and its related diseases.
To understand how glaucoma develops, we must first understand how fluid circulates within the eye. Fluid is produced inside of the eye by a structure known as the ciliary body. This structure is located just beneath the iris. The fluid then travels through the pupil and exits via the eyes drainage system, called the trabecular meshwork.. In healthy eyes, there is a normal balance between the fluid that is made in the eye and the fluid that leaves the eye. Therefore, this fluid creates a relatively constant and healthy pressure within the eye. This pressure is needed to keep the eye inflated, nourished, and functioning properly. This is what we mean by the eye "pressure," and your eye doctor measures it routinely.. ...
PharmOptimas bioanalytical team has extensive experience processing, homogenizing, and extracting ocular fluids and tissues as small as the trabecular meshwork. The company has developed LC-MS/MS methods for hundreds of compounds.. Ocular Matrices Collected:. ...
noun The proper substance of the spleen, contained in the areoles of the trabecular tissue of that organ, forming a soft mass of a dark reddish-brown color, like grumous blood. Also ...
View Nf1/Nf1 Tg(Fabp7-cre,-lacZ)3Gtm/0 involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA: phenotypes, images, diseases, and references.
MIT researchers have developed nanosized antibodies that home in on the meshwork of proteins surrounding cancer cells. This approach could be track tumors as they grow, metastasize or respond to treatment, or as a way to deliver cancer drugs.