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Erbium: YAG laser ablation on human trabecular meshwork by contract delivery endoprobes.

BACKGROUND AND OBJECTIVE: Photoablation of the trabecular meshwork by the infrared laser is an experimental mode of glaucoma surgery. MATERIALS AND METHODS: The authors studied different quartz fiber tips in erbium:YAG laser trabecular ablation. End-firing endoprobes (200 and 320 microns in core diameter) and a side-firing slope tip (200 microns in core diameter) were used. Ablation zones and collateral tissue damage in the trabecular meshwork of human donor eyes were analyzed using light and scanning electron microscopy. RESULTS: The 320-micron end-firing endoprobe most effectively photoablated trabecular tissue by creating large circular craters. The side-firing endoprobe yielded smaller elliptic apertures in the trabecular meshwork. Collateral tissue damage was similar for all endoprobes using pulse energies of 4 and 6 mJ. Transmission impairment was obvious for all quartz fiber tips following frequent use. CONCLUSION: Larger end-firing contact fiberoptic probes provide larger ablation areas in the trabecular meshwork without augmentation of collateral tissue damage.

Erbium↗

[Apoptosis of bovine trabecular meshwork cells induced by dexamethasone].

OBJECTIVE: To investigate apoptosis of bovine trabecular meshwork cells induced by dexamethasone. METHODS: In the incubation method of system in vitro, dexamethasone (1 - 500 mg/L) was added into the syncretic culture solution of the third to fifth generation of bovine trabecular meshwork cells. After 1 - 14 days, the culture solution was observed by phase-contrast microscopy, fluorescence microscopy and transmission electron microscopy, and was studied by DNA laddering and flow cytometric analysis. RESULTS: Dexamethasone (125 - 500 mg/L) induced apoptosis of trabecular meshwork cells in a dose-time-dependent manner. CONCLUSIONS: Apoptosis of cultured bovine trabecular meshwork cells can be induced by dexamethasone, which may be one of the pathogenic mechanisms of steroid-induced glaucoma.

Animals↗

Mechanisms of AAV transduction in glaucoma-associated human trabecular meshwork cells.

BACKGROUND: Glaucoma is a chronic eye disease which leads to irreversible blindness. The trabecular meshwork tissue controls intraocular pressure (IOP), which is the major risk factor for glaucoma. Gene therapy treatment of chronic diseases requires the use of long-term expression, low toxicity and lack of immune response vectors. Adeno-associated viruses (AAV) possess these characteristics but have been unable to transduce the trabecular meshwork. Because of the importance of regulating elevated IOP by long-term gene therapy, we investigated mechanisms of AAV transduction to the human trabecular meshwork (TM). METHODS: Primary human trabecular meshwork cells (HTM) and perfused organ cultures were infected with rAAV2-GFP, RGD-pseudotyped rAAV2-GFP alone, or combined with recombinant DeltaE1/E3 adenoviruses. Intracellular rAAV2 DNA and RNA were measured by relative quantitative and real-time TaqMan polymerase chain reaction (PCR). Host transcriptome was analyzed using high-density oligonucleotide microarrays. One transduction mechanism was tested using self-complementary AAV (scAAV). RESULTS: The dramatic transduction enhancement obtained upon co-infection of rAAV2 with DeltaE1/E3 adenoviruses provides insights into transduction mechanisms in the HTM. Even if not transduced, rAAV2 enters TM cells. GeneChip analysis showed significant changes in host genes involved in cell cycle and DNA replication. Consequently, scAAV-GFP transduction was highly efficient. Other transduction-enhancement genes included coxsackie adenovirus receptor (CAR) and genes relevant to trabecular meshwork function. CONCLUSIONS: The rate-limiting step of AAV transduction was not viral entry failure but, at least in part, host downregulation of DNA replication. Additional specific host genes might be involved. Our study revealed genes and mechanisms which led for the first time to efficient AAV transduction of the HTM.

Anterior Chamber↗

[Targetted ablation of the trabecular meshwork with excimer laser in primary open-angle glaucoma].

The trabecular meshwork and the inner wall of Schlemm's canal constitute 75% of the outflow resistance of the aqueous. Attempts to improve the outflow facility with laser beams have not been satisfactory because they produced thermal effects with coagulation of the trabecular meshwork. With the excimer laser tissue can be removed with minimal thermal effects and necrosis. This results in minimal scar formation. With these qualities the excimer laser lends itself very well for ablation of the trabecular meshwork. It should be possible to create an open connection between the anterior chamber and Schlemm's canal. The goal of our experiments is selected ablation of the trabecular meshwork and the inner wall of Schlemm's canal in order to create pores and enhance the outflow facility. First experiments were carried out on pig and cadaver eyes, followed by eyes destined for enucleation because of malignant melanomas. Finally, we treated 6 patients with open-angle glaucoma. In 4 cases intraocular pressure was reduced by 11 mmHg over a follow-up time of 5 months. In 2 cases IOP rose by 2 mmHg in spite of medication. These preliminary results encourage us to continue with our investigation because there could be a possibility of an effective glaucoma therapy.

Animals↗

Severity of optic nerve damage in eyes with POAG is correlated with changes in the trabecular meshwork.

PURPOSE: We wished to determine whether eyes with primary open-angle glaucoma (POAG) and differing severity of optic nerve damage also have differences in severity of trabecular meshwork changes. METHODS: The trabecular meshwork and optic nerve from 26 eyes (14 donors) with the clinical diagnosis of POAG were studied. Severity of disease ranged from increased intraocular pressure (IOP) without damage to eyes with severe visual field loss. Optic nerve cross-sections were examined with light microscopy, and axonal counts were determined. We studied the trabecular meshwork around the circumference of each eye, examining sections from each quadrant with light and transmission electron microscopy. Morphometric measurements were made of the components of the cribriform region and statistically correlated with the axonal counts by the Pearson correlation coefficient. RESULTS: In eyes with advanced POAG, as determined by visual field loss, measurements of structures in the cribriform region of the trabecular meshwork and axon counts were in the same range as those reported previously in POAG. Axon counts showed a significant negative correlation with the amount of sheath-derived (SD) plaque material in the cribriform region: eyes with lower axon counts had larger amounts of SD plaques. Six eyes from four donors with increased pressure but no clinical signs of optic nerve damage showed no changes in axon counts and no increase in plaque material. CONCLUSIONS: Increasing severity of optic nerve damage in POAG is accompanied by an increase in the amount of SD plaque material in the trabecular meshwork.

Aged↗

A comparison of argon laser and diode laser photocoagulation of the trabecular meshwork to produce the glaucoma monkey model.

PURPOSE: To create an experimental glaucoma monkey model using high-power diode laser photocoagulation of the trabecular meshwork, and to compare this with the experimental glaucoma monkey model induced by argon laser photocoagulation of the trabecular meshwork. METHODS: One eye each of eight adult cynomolgus monkeys underwent repeated application of diode laser photocoagulation of the trabecular meshwork until sustained intraocular pressure (IOP) elevation was achieved. 50 to 120 spots were applied to midtrabecular meshwork for 360 degrees; spot size, 75 microns; power, 1.2 W; duration, 0.5 seconds. Intraocular pressure, tonographic outflow facility, and ophthalmoscopically and photographically documented optic nerve head evaluations were carried out before and after treatment. Data were compared retrospectively with similar data from an experimental glaucoma monkey model after argon laser photocoagulation of the trabecular meshwork (n = 10). RESULTS: The average number of laser treatments to achieve stable IOP elevation was 3.0 with both diode and argon laser trabecular treatments (p > 0.99). On week 4 after initial pressure elevation, peak IOP was greater--(p < 0.05) 43.0 mmHg +/- 2.4 mmHg (mean +/- SEM) and 37.4 mmHg +/- 1.3 mmHg--in the diode laser-induced than in the argon laser-induced glaucomatous eyes, respectively. Outflow facility (microliter/min/mmHg) was reduced (p < 0.001) in both diode (0.09 +/- 0.01 microliter/min/mmHg) and argon (0.10 +/- 0.01 microliter/min/mmHg) laser-induced glaucomatous eyes compared with untreated fellow eyes. Both the diode and argon laser techniques produced the earliest signs of optic nerve head excavation within about one month of IOP elevation. CONCLUSIONS: Repeat diode laser photocoagulation of the trabecular meshwork produced higher (p < 0.05) IOP elevation than argon laser photocoagulation of the trabecular meshwork in this study. No significant differences in outflow facility and optic nerve head change were observed between these two laser techniques. The experimental glaucoma monkey model can be created with either the diode or argon laser photocoagulation of the trabecular meshwork.

Animals↗

Monkey trabecular meshwork cells in culture: growth, morphologic, and biochemical characteristics.

We established tissue cultures of trabecular meshwork cells from cynomolgus monkey eyes. The cultures were initiated within 4 h of enucleation on Falcon Primaria flasks. Using medium containing 10% fetal bovine serum and 5% calf serum, trabecular meshwork cells could be grown for up to eight passages without additional growth factors. The growth pattern and cell morphology were distinct from those seen in fibroblastic or endothelial cultures derived from neighboring tissues. Ultrastructurally, our cells showed the characteristics of trabecular meshwork cells, exhibiting prominent basement membranes, intercellular junctions, pinocytotic vesicles, microvillous projections, and branched cell extensions. These cells were grown mostly as monolayers. However, they also appeared to form multi-layered arrays in densely confluent areas when plated at a high density. The extracellular matrix material was surrounded by cells and cell processes, simulating in vivo trabecular beam formation. Radiolabeling experiments demonstrated that our trabecular meshwork cells had the capacity to produce collagen. These results indicated that our cultured cells retain many in vivo characteristics and may be used for various biologic studies of trabecular meshwork.

Animals↗

Three-dimensional reconstruction of aqueous channels in human trabecular meshwork using light microscopy and confocal microscopy.

Conventional two-dimensional imaging of the trabecular meshwork (TM) provides limited information about the size, shape, and interconnection of the aqueous channels within the meshwork. Understanding the three-dimensional (3-D) relationships of the channels within this tissue may give insight into its normal function and possible changes present in the eye disease glaucoma. The purpose of our study was to compare laser scanning confocal microscopy with standard 1 micron Araldite-embedded histologic sections for 3-D analysis of the trabecular meshwork. In addition, the study was done to determine whether computerized 3-D reconstruction could isolate the fluid spaces of the trabecular meshwork and determine the size of interconnections between the fluid spaces. Confocal microscopy appears comparable to 1 micron Araldite-embedded tissue sections and has the advantage of inherent registration of the serial tissue sections. Three-dimensional reconstruction allowed the isolation of the fluid spaces within the trabecular meshwork and revealed the presence of numerous interconnections between larger fluid spaces. The distribution of these interconnections was randomly arranged, with no predilection for specific regions within the trabecular meshwork. This distribution of constrictions and "expansion chambers" may provide a clue to the mechanism by which subtle histologic changes are associated with increased ocular pressure in glaucoma.

Aqueous Humor↗

[Effect of transforming growth factor beta 2 on phagocytosis in cultured bovine trabecular meshwork cells].

AIM: This study was performed to investigate the effect of transforming growth factor beta 2 (TGF-beta 2) on phagocytosis in bovine trabecular meshwork cells in vitro. METHODS: After cultured bovine trabecular meshwork cells were treated for 24 h with 0 ng/ml (control), 0.32 ng/ml, 1 ng/ml, and 3.2 ng/ml TGF-beta 2, latex beads were added to the incubation medium, and the numbers of latex beads in 20 adjacent cells were then counted under a microscope after treatment with Wright's stain. RESULTS: The average numbers of latex beads in the trabecular meshwork cells treated with TGF-beta 2 of different concentrations were 53.1+/-1.7 beads/cell, 56.4+/-2.9 beads/cell, and 77.9+/-6.5 beads/cell, respectively, compared to 45.5+/-3.3 beads/cell in the nontreated control group. Thus, TGF-beta 2 significantly increased the numbers of latex beads phagocytosed by cultured bovine trabecular meshwork cells in a dose-dependent manner. CONCLUSION: TGF-beta 2 can promote the phagocytosis of bovine trabecular meshwork cells in vitro. It may be involved in the reduced cellularity of the trabecular meshwork in patients with primary open angle glaucoma by promoting the phagocytosis of these cells.

Animals↗

[Dexamethasone inhibits trabecular meshwork cell growth and epidermal growth factor mRNA expression in vitro].

OBJECTIVE: To investigate the effect of dexamethasone on cultured trabecular meshwork cell growth and the cell expression of epidermal growth factor (EGF) mRNA in vitro. METHODS: Human trabecular meshwork cells were cultured in vitro. The third passage cells were used in this experiment; with the addition of 300 microgram/ml dexamethasone in the culture medium in the test group, the culture was carried out as routine. After 5 days, the cell growth conditions were observed. After 7 days, the cells in the test and the control group were collected, and mRNA was drawn from them in both groups. EGFcDNA probe with alpha-(32)P isotope labeling was used to proceed dot blot hybridization and autoradiography to detect EGFmRNA of the cells. A computerized laser instrument was used to scan the size of dot blot hybridization, the relative value of the optical density was measured in the autoradiographs, and the inter-group comparison was made. RESULTS: Trabecular meshwork cells were inhibited by dexamethasone in the test group. The cells in the control group had been confluent at the 5th day, but the cells in the test group still grew like tribes. The total RNA was 14 microgram in the test group, while 22.5 microgram in the control group. In both groups, 14 microgram RNA was used for dot blot hybridization test with EGFcDNA probe. Autoradiographic image was positive in the two groups. The results of the scanning and the measurement of the autoradiograph density showed that dexamethasone obviously decreased the EGFmRNA expression of trabecular meshwork cells. CONCLUSIONS: Dexamethasone can inhibit trabecular meshwork cell growth in vitro. At first it affects the cell total RNA transcription and the second affects the EGFmRMA expression. It is suggested that steroid glaucoma be caused by the inhibition of various physiological and metabolic functions of trabecular meshwork cells induced by dexamethasone.

Adult↗

Effects of ascorbic acid on trabecular meshwork cells in culture.

We examined the effects of ascorbic acid on trabecular meshwork cells in culture. Bovine trabecular meshwork cells were plated for 6 days and were exposed to media containing either no ascorbic acid or ascorbic acid in the following concentrations for 24 hr: 50-, 100-, 500-, and 750 micrograms ml-1. Fresh media were then added and incubation was continued for an additional 24 hr. The cell number was subsequently determined for the effects of the various concentrations of ascorbic acid on cell growth. In a parallel experiment, cells were labeled with [35S] sulfate (50 microCi ml-1) and [3H]glucosamine (15 microCi ml-1) for 24 hr with or without ascorbic acid for glycosaminoglycan studies. Results indicated that ascorbic acid stimulated the trabecular cell growth in culture at concentrations of 50-, 100-, and 250 micrograms ml-1. However, at 750 micrograms ml-1, cell growth was inhibited. In addition, cells exposed to 100 micrograms ml-1 of ascorbic acid demonstrated increased incorporation of [3H]glucosamine and [35S]sulfate; enhancement of incorporation of [35S]sulfate was also noted at 250 micrograms ml-1. Incorporation of labels was otherwise either unchanged or retarded at other concentrations. These data suggest that the ascorbic acid level in the aqueous humour may influence trabecular meshwork cell metabolism.

Animals↗

Apoptosis and morphologic changes in drug-treated trabecular meshwork cells in vitro.

Using an in vitro culture system, we investigated whether bovine trabecular meshwork cells undergo apoptosis (programmed cell death) following exposure to anti-glaucoma medications (timolol, pilocarpine and epinephrine) and known inducers of apoptosis (5-fluorouracil, mitomycin-C and dexamethasone). Third to fifth passage bovine trabecular meshwork cells were grown to confluence and incubated for 1-12 days in growth media with timolol (1-1000 microM), pilocarpine (15-15,000 microM), epinephrine (5-5000 microM), 5-fluorouracil (10-100 micrograms ml-1), mitomycin-C (0.01-100 micrograms ml-1) and dexamethasone (0.01-100 microM). The cultures were evaluated for apoptosis by phase-contrast microscopy, transmission electron microscopy and in situ apoptosis labeling. 5-Fluorouracil (10-100 micrograms ml-1), mitomycin-C (0.1-100 micrograms ml-1) and epinephrine (500-5000 microM) induced apoptosis in a dose and time-dependent manner. Timolol, pilocarpine, and dexamethasone-treated specimens did not show evidence of apoptosis at any of the concentrations tested. Trabecular meshwork cells incubated in timolol (100-1000 microM) developed cytoplasmic granules, and specimens treated with pilocarpine (15,000 microM) developed cytoplasmic vacuoles. These granules and vacuoles have the appearance of secondary lysosomes. Dexamethasone-treated cells developed an increased number of mitochondria. This study suggests that the trabecular meshwork may undergo apoptosis following exposure to 5-fluorouracil, mitomycin-C and epinephrine. Timolol, pilocarpine and dexamethasone did not induce apoptosis. However, these drugs can incite characteristic morphologic changes in cultured trabecular meshwork cells.

Animals↗

In situ localization of cytoskeletal elements in the human trabecular meshwork and cornea.

The authors compared cytoskeletal elements of the in situ human trabecular-meshwork cell with in situ human corneal cells using indirect immunofluorescence staining for tubulin and intermediate filaments (vimentin, cytokeratin, and desmin) and NBD-phallacidin staining for f-actin using both fixed frozen and unfixed frozen sections from postmortem eyes. Both f-actin and tubulin were found throughout the cell body of trabecular-meshwork cells, keratocytes, corneal endothelium, and corneal epithelium. The f-actin staining pattern was concentrated at the cell periphery of these four cell types. Vimentin stain was intensely localized in focal areas of the trabecular-meshwork cell, keratocytes, and throughout the corneal endothelium. A general anticytokeratin antibody was intensely localized in corneal epithelium and endothelium. However, PKK-1 anticytokeratin antibody was seen only in superficial layers of corneal epithelium and not in corneal endothelium. The 4.62 anticytokeratin antibody was not observed in either corneal epithelium or endothelium. None of these three cytokeratin antibodies were seen in trabecular-meshwork cells or keratocytes. Desmin stain was not noted in any of these cell types. In general, cytoskeletal staining of unfixed frozen sections showed a similar staining pattern for f-actin and tubulin but a more uniform and intense staining pattern for vimentin and cytokeratin compared with fixed frozen material. The authors conclude that these cytoskeletal stains can differentiate human trabecular-meshwork cells from cells of the cornea in situ.

Actins↗

Direct involvement of trabecular meshwork in the regulation of aqueous humor outflow.

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.

Animals↗

Barriers to productive transfection of trabecular meshwork cells.

PURPOSE: A critical function of trabecular meshwork cells is to degrade cellular debris, including DNA. We hypothesize that low transfection efficiencies of primary human trabecular meshwork (HTM) cell cultures with plasmid DNA are a function of retained capacity to efficiently degrade exogenous DNA in vitro. METHODS: To determine mechanisms responsible for low transfection efficiencies of cultured HTM cells, steps of DNA entry into cytoplasm and nucleus were characterized. Following synchronization with sequential serum starvation and serum reintroduction, the HTM cell cycle was characterized using 5-bromo-2-deoxyuridine incorporation into replicating DNA. HTM cells were transfected during S-phase with plasmid DNA encoding green fluorescence protein (GFP) or plasmid DNA conjugated with Cy3. In some experiments, cells were treated with a DNase I inhibitor, 100 nM aurintricarboxylic acid. Uptake of plasmid DNA was measured by intracellular fluorescence of Cy3 and productive transfection efficiency was measured by intracellular fluorescence of GFP. RESULTS: HTM cells enter S-phase between 18 and 20 h after synchronization. Plasmid DNA reached the cytosolic compartment in 95% of transfected cells, regardless of synchronization. Synchronization dramatically increased productive transfection efficiency in HTM cells, from 3.0 to 9.0%. DNase I inhibition increased productive transfection efficiency of HTM cells two fold. CONCLUSIONS: Cultured HTM cells have a lower transfection efficiency than other primary ocular cell cultures, likely due partially to cytoplasmic digestion of DNA. We suggest that the difficulties in transfecting cultured HTM cells may be related to the filter function of the cells in vivo where the cells must degrade exogenous DNA.

Adult↗

Phagocytosis by trabecular meshwork cells: sequence of events in cats and monkeys.

Trabecular meshwork cells have well-established phagocytic properties. However, the sequential stages of this process have not been studied in detail. Zymosan particles, yeast cell walls 3 micron in diameter, were either injected or perfused into the anterior chambers (AC) of cats and monkeys. Glutaraldehyde (3%) was then infused into the AC at 1-, 6-, 17-, 30- and 60 min and the fate of the particles observed by transmission electron microscopy. After contact with zymosan particles, trabecular meshwork cells demonstrated short cytoplasmic extensions at contact sites and an increased number of cytoplasmic organelles. Internalization of the particles occurred by 6 min in the cat and by 17 min in the monkey. In both species similar events occurred following internalization of zymosan: trabecular cells, laden with particles, rounded up, detached from their underlying collagenous beams and migrated towards Schlemm's canal or the aqueous plexus. By 1 hr the individual trabecular cells completed the entire sequence of phagocytic events although some cells were always observed in earlier stages of the process. These data document for the first time the timing of the cellular events that take place during zymosan particle phagocytosis by trabecular meshwork cells.

Animals↗

Endothelin-evoked contractions in bovine ciliary muscle and trabecular meshwork: interaction with calcium, nifedipine and nickel.

In the present study, we compared contractile responses of isolated bovine ciliary muscle and trabecular meshwork strips to endothelin-1 and carbachol. 1. Endothelin-1 is a potent contracting agent for ciliary muscle and trabecular meshwork. The EC50 was 5 x 10(-9) mol/l for both tissues. The maximal force evoked by endothelin was 73% of the maximal carbachol response in trabecular meshwork and 52% in ciliary muscle. 2. Carbachol contracted both tissues with an EC50 of 2 x 10(-7) mol/l. 3. In ciliary muscle, the tension was completely dependent on extracellular calcium. 4. In trabecular meshwork, 23 +/- 4% of the endothelin- and 42 +/- 10% of the carbachol-induced force response remained after removal of extracellular calcium. 5. Nifedipine (10(-5) mol/l) had only a slight relaxing effect in both tissues. 6. Nickel (10(3) mol/l) inhibited the development of force in both tissues. The relaxation induced by nickel was more pronounced in endothelin- than in carbachol-induced contractions. Different intracellular mechanisms mediating the action of endothelin and carbachol can be described: i) a calcium- and a nickel-sensitive pathway in both tissues and ii) an additional mechanism independent of external calcium in trabecular meshwork. These results indicate functional differences between the contractile region of trabecular meshwork and ciliary muscle. Endothelin may participate in accommodation and regulation of the intraocular pressure.

Animals↗

Antagonistic effects of tranilast on proliferation and collagen synthesis induced by TGF-beta2 in cultured human trabecular meshwork cells.

Whether tranilast had antagonistic effect on proliferation inhibition and collagen synthesis promotion induced by TGF-beta2 in cultured human trabecular meshwork cells was investigated. Suspension of 1 x 10(4) cultured human trabecular meshwork cells of 3-5 passage was distributed in each well of a 96-well disk and divided into control group and experimental group. After 24 h, 0 microg/ml (control), 12.5 microg/ml, 25 microg/ml, 50 microg/ml tranilast with 3.2 ng/ml TGF-beta2 were added into the incubation medium. Another 24 h later, proliferation and collagen synthesis in cultured human trabecular meshwork cells were examined respectively by using tetrazolium-based semiautomated colormetric (MTT) assay and 3H-proline incorporation with liquid scintillation technique. The results showed absorbance (A) values of the experimental groups were 0.9036 +/- 0.3017, 1.1361 +/-0.1352, 1.2457 +/- 0.1524 according to the different concentrations of tranilast, and 0.8956 +/-0.1903 of the control group. In comparison with the control group, 25 microg/ml (q'= 3.23, P< 0.05), 50 microg/ml (q'=4.70, P<0.01) tranilast significantly antagonized the decrease of the A values induced by TGF-beta2 in the cultured human trabecular meshwork cells. In comparison with the control group [817.37+/-124.21 cpm/10(4) cells], 12.5 microg/ml (620.33+/-80.46 cpm/10(4) cells, q'= 4.26, P<0.05), 25 microg/ml (594.58+/-88.13 cpm/10(4) cells, q'=4.81, P<0.01), 50 microg/ml (418.64+/-67.90 cpm/10(4) cells, q'=8.62, P<0.01) tranilast significantly inhibited the incorporation of 3H-proline into the cultured human trabecular meshwork cells promoted by TGF-beta2 in a dose-dependent manner. It was concluded that tranilast had the antagonistic effect on the proliferation inhibition and collagen synthesis promotion induced by TGF-alpha2 in the cultured human trabecular meshwork cells.

Cell Proliferation↗