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Trabeculotomy in pseudoexfoliation of the lens capsule.

Trabeculotomy was performed on 12 eyes of 11 patients with glaucoma associated with pseudoexfoliation of the lens capsule. Pressure was lowered in all eyes, in 10 eyes to 15 mmHg or less, 7 with no medication but 3 with medication. A subconjunctival bleb was present in 5 patients but was not necessary for a good result. These results suggest that the raised intraocular pressure which often occurs in pseudoexfoliation of the lens capsule is due to interference with flow of aqueous across the trabecular meshwork. Trabeculotomy seems a safe and effective operation in glaucoma associated with pseudoexfoliation of the lens capsule.

Aged↗

The production and mechanism of ghost cell glaucoma in the cat and primate.

Fresh human ghost blood cells (GBCs) have been shown to cause increased resistance to outflow in enucleated human eyes. In addition, glutaraldehyde-fixed GBCs can cause glaucoma in the rabbit and primate in vivo. The present study shows for the first time that fresh autologous GBCs can cause an acute in vivo rise of intraocular pressure when injected into the anterior chambers of the cat and primate. This rise was of greater magnitude and longer duration than that caused by the injection of a greater number of pliable, fresh red blood cells. It has been theorized that ghost cell glaucoma (GCG) is due to cellular obstruction of the intertrabecular spaces by the nonpliable GBCs. Histologic results from the present study confirm this belief. No evidence of significant trabecular meshwork degeneration or significant GBC phagocytosis was seen.

Animals↗

Histopathologic verification of position of laser burns in argon laser trabeculoplasty.

Surgical trabeculectomy was performed on 10 eyes of 10 patients following failure of argon laser trabeculoplasty. All specimens were examined by scanning electron microscopy to determine anatomic location of laser damage. Correlation with clinical data revealed accurate placement of laser burns in 11 out of 13 treatment sessions. The degree of laser injury varied with energy delivered and pigmentation of the posterior trabecular meshwork. Complications such as corneal endothelial, oblique, and confluent burns were present in 50% of cases studied.

Argon↗

Concentration-dependent morphologic effects of cytochalasin B in the aqueous outflow system.

Cytochalasin B at concentrations of 1, 5, 10, 15, 20, or 40 microgram/ml was continuously exchange-perfused into the eyes of nine living Macaca mulatta monkeys while intraocular pressure (IOP) was maintained at 25 mm Hg for 30 min. Pressures were then slowly reduced to 4 mm Hg to permit blood to reflux into Schlemm's canal as a tracer, and the eyes were fixed while maintained at 4 mm Hg IOP. Tissues were examined in all eyes by light and transmission electron microscopy. At concentrations of 1, 5, and 10 microgram/ml cytochalasin B, the integrity of the endothelial lining of the trabecular wall of Schlemm's canal was maintained. At 15 microgram/ml cytochalasin B, 6% of the length of the endothelial lining was disrupted; at 20 microgram/ml, 54%; and at 40 microgram/ml, 83%. There was a washout of extracellular material at the site of breaks and also a reflux of blood from Schlemm's canal into the trabecular meshwork in the same regions.

Animals↗

The ultrastructural changes in the exfoliation syndrome.

Exfoliation fibrils have a characteristic ultramicroscopic appearance. They are 20-30 nm thick with 10 nm subunits and may be 800 or 900 nm long. They sometimes have a characteristic banding periodicity of about 50 nm. The fibrils have been located in the lens capsule, zonular threads, iris, ciliary body and trabecular meshwork. Extraocular locations have also been found in conjunctival vessels and retroorbital tissue.

Anterior Eye Segment↗

Effect of staurosporine on outflow facility in monkeys.

PURPOSE: To determine the effect of the serine-threonine kinase inhibitor staurosporine on outflow facility in living monkeys. METHODS: Total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber bilaterally before and after intracameral infusion of staurosporine or vehicle in opposite eyes. RESULTS: Intracameral staurosporine dose-dependently doubled outflow facility, with 0.1 microM, 1 microM, and 10 microM being subthreshold, effective, and maximal doses, respectively. At 50 microM, intracameral staurosporine was less effective than 10 microM on facility and induced corneal toxicity. CONCLUSIONS: The broad-spectrum protein kinase inhibitor staurosporine increases outflow facility in living monkeys, perhaps by affecting the trabecular meshwork cytoskeleton.

Animals↗

[Retinitis pigmentosa associated with glaucoma].

Analysis of 1400 cases of retinitis pigmentosa revealed that (1) 32 cases (2.3%) were associated with glaucoma, of which (2) 30 cases were of the angle closure type; (3) the C/D ratio was normal in over one half of the cases, and in 5 cases the optic disk remained normal after 1/2-5 years of persistent IOP elevation; (4) in 31 cases (97%) the blood pressure was below the norm of equivalent age group; and (5) pathologic examination of the trabecular meshwork in 14 cases showed no excessive pigment deposition to obstruct the outflow channels.

Adolescent↗

[The effects of a new type of laser on fixed tissue of the angle of the anterior chamber in the monkey eye (author's transl)].

Segments of fixed tissue of the chamber angle of the monkey eye are irradiated with a neodymium (YAG-) q-spoiled laser at a pulse duration of 50 ns, a pulse energy of 200 mJ and an optic distance of 15 mm. Perforating injuries are observed between the anterior chamber and Schlemm's canal. When an acute angle of the laser beam relative to the cornea is chosen, the application point must be at the anterior part of the trabecular meshwork, close to the cornea, to open the canal of Schlemm. An impact further back toward the iris would create cyclodialysis.

Animals↗

Ocular hypertension following Nd:YAG laser capsulotomy: a potentially blinding complication.

A dense secondary membrane was treated with a Nd:YAG laser capsulotomy with marked improvement in visual acuity, from count fingers to 6/9 (20/40). Four hours following therapy, visual acuity in the treated eye was no light perception, due to extreme ocular hypertension (over 80 mm Hg). The extreme elevation in intraocular pressure appears to have been caused by cellular debris obstructing the trabecular meshwork in an angle already compromised by angle recession. An emergency paracentesis was successful in restoring the visual acuity.

Adult↗

Monkey organ-cultured anterior segments: technique and response to H-7.

In the intact primate eye in vivo, it may be difficult to determine whether an outflow facility response is due to direct effects on the trabecular meshwork or indirectly via an effect on ciliary muscle tone unless complicated surgical ciliary muscle disinsertion or isotope accumulation procedures are used. We established a monkey anterior segment organ culture system modeled after the human anterior segment organ culture system and determined its characteristics and response to H-7, an agent shown to increase trabecular outflow in vivo and in other organ culture systems. Outflow facility studies conducted using the monkey organ-cultured anterior segment system showed that: baseline values were comparable to those measured in vivo; washout occurred with time; the two-level constant pressure perfusion technique gave results comparable to the constant rate technique; species differences were found comparing baseline outflow facility and intraocular pressure in rhesus and cynomolgus monkey organ-cultured anterior segments; there was no effect of age on outflow facility in either species by one-way ANOVA; anterior segment exchange perfusion increased outflow facility if measured within 1 hr of the exchange; the magnitude of the response to H-7 was comparable to those reported in vivo and in other in vitro systems. The onset of the response to H-7 was delayed in most cases (day after H-7 exchange), compared to in vivo monkey studies (onset 6-9 min) and in vitro human and porcine organ culture systems (within 1 hr). Also the duration of the response (2-3 days from the onset) was longer than that found for in vitro human studies (1 day). Thus, the monkey organ-cultured anterior segment system can be used to determine the effects of pharmacological and biological agents on trabecular outflow.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Repeated argon laser trabeculoplasty.

In 20 eyes (18 patients) with simple or capsular glaucoma in which a first full-circumference argon laser trabeculoplasty resulted in early or late failure, laser trabeculoplasty was repeated. In 12 eyes the second trabeculoplasty was clinically successful. At an average follow-up time of 30 months after second trabeculoplasty, the treatment was still successful in six patients. Early failure after the first treatment seems to be unfavourable for the outcome of secondary treatment. No correlation was found between the accumulated dose of laser energy delivered into the trabecular meshwork and the degree of intraocular pressure reduction after the second trabeculoplasty in this retrospective study.

Aged↗

Pigmentary glaucoma associated with posterior chamber intraocular lenses.

Six cases of glaucoma associated with pigment dispersion syndrome occurred after the implantation of posterior chamber intraocular lenses. All six patients had iris transillumination defects associated with the intraocular lens haptics, increased intraocular pressure, and pigment deposition in the trabecular meshwork and the anterior chamber. Medication controlled the glaucoma and none of the patients required further surgery.

Aged↗

Effects of time of storage, albumin, and osmolality changes on outflow facility (C) of bovine anterior segment in vitro.

PURPOSE: To analyze the influence of time of storage, the presence of albumin at physiological concentrations, and the perfusion with anisosmotic media on the aqueous humor outflow facility (C) of isolated bovine anterior segments (AS). METHODS: Anterior segments dissected from cow eyes were perfused at a constant pressure of 10 mm Hg with Dulbecco's modified Eagle's medium (DMEM; osmolality 300 mOsm/kg), with hyposmotic media (150, 210, and 270 mOsm/kg), or with hyperosmotic media (360, 420, and 480 mOsm/kg). Outflow facility was calculated every 5 seconds as the ratio between average inflow from the reservoir (in microliters per minute) and the perfusion pressure (in millimeters of mercury). Three groups were studied: a 0-hour group, with AS perfused with DMEM 1 to 3 hours after enucleation; a 0-hour alb-group, with AS perfused with DMEM plus 0.1 mg/ml albumin 1 to 3 hours after enucleation; and a 24-hour group, with AS perfused after storage for 24 hours in DMEM. In the 0-hour groups, perfusion with increasingly hyposmotic or hyperosmotic media was also made in 30-minute steps, followed by a return to isosmotic medium for 90 minutes. RESULTS: Perfusion of AS with DMEM for 9 hours caused a progressive increase in C that was statistically significant at 225 minutes in the 0-hour group perfused with DMEM and at 195 minutes in the 24-hour group perfused with DMEM. The 0-hour alb-group perfused with DMEM did not show changes in C throughout the 9-hour perfusion period. Perfusion with increasingly hyposmotic media induced a progressive decrease in C that did not recover on return to isotonic medium. Hyperosmotic media caused a progressive increase in C that returned to control values when isotonic medium was again perfused. CONCLUSIONS: Preservation of tissue for C measurements is best achieved with short storage time (1 to 3 hours). Physiological concentrations of albumin (0.1 mg/ml) prevent development of washout, suggesting that albumin or an albumin-bound factor in aqueous humor may play a role in the maintenance of outflow resistance. Outflow facility also may be influenced by volume changes in the trabecular meshwork.

Animals↗

Transient open-angle glaucoma associated with sickle cell trait: report of 4 cases.

Four black patients, all with sickle trait (SA), developed transient open-angle glaucoma with blood in Schlemm's canal. In 3 patients the condition followed blunt trauma, while in the fourth no antecedent trauma was described. The intraocular pressure became normal in all 4 cases with the resolution of the haemorrhage from the trabecular meshwork and Schlemm's canal.

Adult↗

Aqueous humor dynamics in monkeys after topical 8-iso PGE(2).

PURPOSE: To determine in normotensive cynomolgus monkeys, the effects of topical 8-iso prostaglandin (PG)E(2) on intraocular pressure (IOP), aqueous humor formation (AHF), uveoscleral outflow (Fu), and total and trabecular outflow facility. METHODS: IOP was measured by Goldmann applanation tonometry under ketamine anesthesia after single or twice-daily topical treatments with 8-iso PGE(2). With animals under pentobarbital anesthesia, AHF and flow to blood (equated to trabecular outflow) were determined by anterior chamber perfusion with radioactively labeled albumin solution. Fu and trabecular outflow facility were calculated from these measurements. Total outflow facility was measured by two-level, constant-pressure perfusion. RESULTS: IOP was not significantly changed after single or multiple 10- micro g doses of 8-iso PGE(2). The 25- micro g dose significantly decreased IOP by 2 to 3 mm Hg compared to the contralateral vehicle-treated control 4 to 6 hours after a single dose and by 3 to 5 mm Hg within 1.5 hours after twice-daily treatments for 4 to 5 days. Total outflow facility corrected for control eye washout was increased by an apparent 37% (P < 0.02, n = 7) from 2 to 3.5 hours after the ninth dose, largely due to outlier values obtained in one monkey. Isotope studies performed after twice-daily treatments totaling 9 to 29 doses showed no change in AHF, trabecular outflow facility, or total outflow facility. Relative to AHF, trabecular outflow was significantly decreased, and the calculated Fu was significantly increased when all data were analyzed. CONCLUSIONS: The present findings are consistent with lowering of IOP by 8-iso PGE(2), primarily by increasing Fu. A direct effect on the trabecular meshwork was not indicated by these in vivo studies.

Administration, Topical↗

Identification and partial characterization of TGF-beta 1 receptors on trabecular cells.

By using two specific receptor assays, we identified and partially characterized receptors for transforming growth factor-beta 1 (TGF-beta 1) on porcine trabecular cells in vitro. Cultured trabecular cells were incubated with labeled TGF-beta 1 and analyzed by flow cytometry. Pretreatment with trypsin or preincubation with cold TGF-beta 1 or a neutralizing antibody to TGF-beta 1 inhibited the binding of labeled TGF-beta 1. 125I-TGF-beta 1 was cross-linked covalently to cell surface receptors on the trabecular cells. By SDS-PAGE and autoradiography, we identified three labeled macromolecular species of receptors, two of which had apparent molecular weights greater than 212 kDa and one of which had an apparent molecular weight of approximately 80-90 kDa under reducing conditions. The low and high molecular weight species probably represent type II and type III TGF-beta 1 receptors, respectively. At concentrations of 0.5 and 1 ng/ml, activated TGF-beta 1 caused retraction and a marked decrease in the rate of proliferation and in the motility of trabecular cells in vitro. Our findings implicate TGF-beta 1 in the modulation of the functional homeostasis of trabecular cells and suggest that the aqueous humor contains a level of TGF-beta 1 which, once activated, is sufficient to exert a biologic effect on the trabecular meshwork.

Animals↗

Involvement of protein kinase C in TNFalpha regulation of trabecular matrix metalloproteinases and TIMPs.

PURPOSE: The cytokine TNFalpha is a strong modulator of trabecular meshwork (TM) matrix metalloproteinase (MMP) and tissue inhibitor (TIMP) expression. Studies were conducted to identify signal-transduction pathways involved. METHODS: Porcine TM cells were treated with TNFalpha, and MMP and TIMP levels were evaluated by zymography and Western immunoblot. Inhibitors and activators of several signal-transduction pathways were used to select pathways that could be involved. Trabecular protein kinase C (PKC) isoforms were identified and localized by using Western immunoblots and confocal immunohistochemistry. Changes in subcellular distribution of PKC isoforms were evaluated. PKC isoform downregulation and additional inhibition profiles were used to refine the involvement pattern of different isoforms. RESULTS: TNFalpha treatment increased MMP-1, -3, and -9 and TIMP-1 expression, whereas MMP-2 expression was not affected and TIMP-2 expression decreased. Agents that modulate protein kinase A (PKA) or inhibit phosphatidylinositol 3-kinase (PI3K) had minimal effects on trabecular MMP or TIMP induction by TNFalpha, whereas several agents that modulate PKC activity were effective. Trabecular cells expressed several PKC isoforms, which exhibited distinctive subcellular localization. TNFalpha treatment triggered some PKC isoform translocations. Exposure of trabecular cells to TNFalpha for 72 hours differentially downregulated several PKC isoforms. Treatment with a phorbol mitogen that stimulates most PKC isoforms produced strong increases in these MMPs. TNFalpha's effects on MMP and TIMP expression were completely blocked by only one PKC inhibitor. CONCLUSIONS: The PKA and PI3K pathways appear not to be involved directly in transducing this TNFalpha signal, but at least one isoform of PKC seems to be required. Based on the inhibitor profiles and the downregulation and translocation studies, PKC(mu) appears to be critical in transducing this signal. Unraveling the remaining steps in this and in additional related TM signal-transduction pathways may provide targets for developing improved glaucoma treatments.

Blotting, Western↗

The appearance of the outflow apparatus of the eye after staining with ruthenium red.

The outflow apparatus from adult baboon and rabbit eyes was stained with the inorganic dye ruthenium red. The ruthenium reaction product coated the surface of the trabecular meshwork cells and the canalicular endothelial cells. Deposits also impregnated the various connective tissue elements within the trabeculae and the extracellular spaces of the endothelial meshwork. A fine fibrillar network could also be identified with ruthenium red and this was present in the trabecular cores and the extracellular spaces of the endothelial meshwork. It was considered that the fibrillar network may represent a matrix of glycosaminoglycans and glycoproteins. The significance of these materials in relation to aqueous outflow was discussed.

Animals↗