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PubMed2003

Acute ultrastructural changes of the trabecular meshwork after selective laser trabeculoplasty and low power argon laser trabeculoplasty.

BACKGROUND AND OBJECTIVES: To compare the histopathological changes in the human trabecular meshwork after low power argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) with a Q-switched, frequency-doubled, neodymium:yttrium-aluminium-garnet (Nd:YAG) laser. STUDY DESIGN/MATERIALS AND METHODS: In gonioscopically normal trabecular meshwork of three patients awaiting enucleation due to malignant melanoma of the choroid, SLT and ALT were performed 1-5 days prior to enucleation. In each eye, the lower half of trabecular meshwork received SLT, one quadrant low power (460 mW) ALT and one quadrant was left untreated. Specimens were evaluated with light and transmission electron microscopy. RESULTS: A sharp demarcation line was visible between the laser treated and untreated intact trabecular meshwork after ALT and SLT. Both lasers caused disruption of trabecular beams, but the extent of the damage was smaller after SLT. The collagen component of trabecular beams was mostly amorphous, the long-spacing collagen was scanty after ALT, but more abundant after SLT. In the intertrabecular spaces fragmented cells and tissue debris with only a few pigmented cells were observed. Some endothelial cells were desquamated, but appeared slightly better preserved after SLT than ALT. CONCLUSIONS: Our ultrastructural comparison of the morphological changes after low power ALT and SLT in patients demonstrated that both lasers caused splitting and fragmentation of the trabecular beams of the trabecular meshwork, but the extent of the damage was smaller and the preservation of long-spacing collagen better after SLT than after ALT.

Argon↗
PubMed2006

Ultrastructure of the trabecular meshwork in secondary glaucoma eyes after intravitreal triamcinolone acetonide.

PURPOSE: To study the histology of the trabecular meshwork of eyes with glaucoma by intravitreal injection of triamcinolone acetonide (TA). DESIGN: Two cases report. PARTICIPANTS/METHODS: A 68-year-old Japanese man with branch retinal vein occlusion and a 48-year-old Japanese woman with uveitis were treated by cataract surgery, intraocular lens implantation, and TA-assisted pars plana vitrectomy. At the end of surgery, TA suspension (4 mg) was intravitreously injected. During the follow-up period, the intraocular pressure (IOP) of the patients increased over 30 mm Hg even with full medication. Trabeculectomy was performed at 4 months after TA injection in case 1 and at 6 months in case 2, and intraocular pressure returned to the normal range in both cases. Light and electron microscopic studies of the resected trabecular tissue were carried out. RESULTS: The histology showed minimal deposition of extracellular matrix in the trabecular meshwork in case 1. Case 2 showed the beginnings of deposition of extracellular matrix including fingerprintlike material in the trabecular meshwork with decreased intertrabecular spaces. CONCLUSIONS: The ultrastructural changes in the trabecular meshwork of eyes with glaucoma after treatment with intravitreal TA might resemble those with glaucoma after topical corticosteroid treatment.

Extracellular Matrix↗
PubMed1984

Effects of chondroitin sulfate on metabolism of trabecular meshwork.

Glycosaminoglycans are believed to play a role in the physiological functions of trabecular meshwork. The effects of chondroitin sulfate on the metabolism of trabecular meshwork were studied by replacing the aqueous humor in the right eye (experimental eye) of 12 albino rabbits with 0.3 ml of chondroitin-4-sulfate solution (10 mg ml-1 in glucose-supplemented phosphate buffered saline). The aqueous humor in the left eye (control eye) was replaced with the phosphate buffered saline-glucose solution in the same manner. The intracameral procedures were performed twice a week for four weeks (initial injection period), and then discontinued for another four weeks (resting period). No significant or prolonged increase in the intraocular pressure was observed during either period in any eyes. Subsequent intracameral injections performed after the resting period, however, caused an intraocular pressure elevation in 10 of the 12 experimental eyes. During this second injection period, the injections were carried out whenever the intraocular pressure of experimental eyes dropped to the control value. The pressure generally remained 5-10 mmHg above that of the control eyes for periods ranging from two days to four weeks. In the eyes with elevated intraocular pressure, light microscopy showed that the trabecular beams were compact and sclerotic and the intertrabecular spaces were narrower. Chamber angle tissues obtained from the eyes with elevated intraocular pressure incorporated more radioactive precursors into glycosaminoglycans than those from the control eyes. The synthesis of glycosaminoglycans and the metabolism of trabecular meshwork seemed to be modified by the long-term chondroitin sulfate treatment.

Animals↗
PubMed2000

Expression of the TIGR gene in the iris, ciliary body, and trabecular meshwork of the human eye.

Mutations in the the glaucoma gene GCL1A, also known as trabecular meshwork glucocorticoid response (TIGR) or myocilin (Myoc), have been shown to be associated with juvenile-onset primary open-angle glaucoma. Very little is known about the pattern of expression of the TIGR gene in human ocular tissues. In-situ hybridization experiments demonstrated the localization of TIGR mRNA in cells throughout the iris, ciliary muscle, and the filtering portion of the trabecular meshwork of normal eye donors. The expression of TIGR protein was investigated by Western blot using an epitope-directed antibody to the carboxy terminus region of TIGR. This antibody was able to distinguish a recombinant TIGR fusion protein from a truncated TIGR form containing the naturally occurring Gln(368)-->stop mutation. In tissue extracts from the iris, ciliary body, and trabecular meshwork, the antibody recognized a major protein band of 57-kDa molecular mass. Deglycosylation treatment with PNGase F, NANase II, and O-glycosidase indicated that the 57-kDa protein in these tissues was unglycosylated. In agreement with this observation, in coupled in-vitro transcription/translation systems, the 57-kDa TIGR protein was unaffected by the presence of the processing and glycosylation activities of canine pancreatic microsomal membranes. These findings support the view that the expression of TIGR mRNA in cells of the iris, ciliary body, and trabecular meshwork correlates with that of TIGR protein, and that the 57-kDa TIGR protein was unglycosylated. These results, which are in contrast with earlier reports, raise the possibility that the TIGR protein might be processed into distinct forms in a tissue-specific manner.

Adult↗
PubMed2000

Distribution of peptidergic nerve fibres in the guinea pig trabecular meshwork.

A quantitative analysis of peptidergic nerve fibres located in the trabecular meshwork of the guinea pig has been performed. Our results confirm that this structure contains VIP-, NPY- and substance P-like immunoreactivity as major neurotransmitters. These findings were obtained using immunohistochemical techniques. For this purpose serial sections of the eye were stained by immunohistochemistry for each of three neurotransmitters and stained sections were analysed by quantitative image analysis. Our findings demonstrate that SP-positive, NPY-positive and VIP-positive nerve fibres occupy 11.2, 4.9 and 2.4%, respectively, of the observed area (expressed as conventional units, C.U.) in the trabecular meshwork of the guinea pig eye. It is relevant to emphasize that the area containing these three types of peptidergic nerve fibres appears to be large (18.5 +/- 6.6 C.U.) in proportion to the total observed area. The innervation of the drainage angle of the guinea pig eye has been well described by many authors. This is the first study to report quantitative measurements of three types of peptidergic nerve fibres identified and measured in this area. The presence of these three neurotransmitters in the trabecular meshwork of guinea pig eye suggests their possible participation in aqueous humor regulation.

Animals↗
PubMed1985

Superoxide dismutase and catalase of calf trabecular meshwork.

Superoxide dismutase and catalase activities have been measured in cell-free extracts of calf trabecular meshwork, and for comparison, in calf iris, retina, lens, liver, and erythrocytes. Gel electrophoresis has been used to identify isozymes of each enzyme. The superoxide dismutase and catalase activities per milligram wet weight of calf trabecular meshwork, 0.184 and 0.884 U/mg wet wt, respectively, were comparable to those found in iris and retina, and much higher than those found in lens. Three isozymes of superoxide dismutase were identified in trabecular meshwork. Two of these presumably correspond to cytoplasmic superoxide dismutase, while the third corresponds to a mitochondrial isozyme. A presumably mitochondrial superoxide dismutase activity was also observed in iris and retina, but not in lens. A single catalase isozyme was found in all tissues examined. At physiologic H2O2 concentrations, catalase may have similar levels of activity to glutathione peroxidase. Superoxide dismutase, catalase, and glutathione peroxidase may constitute an important defense mechanism of trabecular meshwork against the toxic O2-. and H2O2 to which it must be continuously exposed from endogenous production as well as from the aqueous humor.

Animals↗
PubMed1988

Arachidonic acid metabolism in human trabecular meshwork cells.

Prostaglandins and other eicosanoids in the trabecular meshwork may play important physiological and pharmacological roles in the aqueous outflow pathway. In the present studies, we employed [14C]-arachidonic acid to explore potentially important pathways for the production of eicosanoids in cultured human trabecular meshwork cells (HTM). In these cells, we demonstrated that prostaglandin E2 (PGE2) and PGF2 alpha are major cyclooxygenase products, with some 6-keto-PGF1 alpha also detected. The amount of radiolabelled PGE2 formed was substantially higher than the PGF2 alpha formed in the early time periods. The amount of PGF2 alpha in the culture media increased at a time when the amount of PGE2 was declining, suggesting a possible metabolic conversion between the prostaglandins. HTM produced a range of products of the lipoxygenase pathway. Products co-eluting with 5, 12, and 15-hydroxyeicosatetraenoic acids (HETEs) were detected, with 12 and 15-HETEs predominating. A large amount of radiolabelled product was detected also in peaks co-eluting with leukotriene B4 (LTB4) and an LTB4 degradation product. Biosynthesis of lipoxygenase products was markedly inhibited by BW 755c and partially inhibited by dexamethasone. These data emphasize that HTM cells are capable of converting arachidonic acid into a wider variety of biologically active products than previously recognized.

Arachidonic Acid↗
PubMed2004

Muscarinic receptor agonists protect cultured bovine trabecular meshwork cells against apoptosis induced by dexamethasone.

PURPOSE: To study whether muscarinic receptor agonists can protect cultured bovine trabecular meshwork cells against apoptosis induced by dexamethasone. METHODS: The third to fifth passages of bovine trabecular meshwork cells were grown to confluence and incubated for 1-14 days in growth media with dexamethasone or pretreatment of pilocarpine or carbachol. The cultures were evaluated for apoptosis by phase-contrast microscopy, fluorescence microscopy, DNA laddering and flow cytometric analysis. RESULTS: Dexamethasone (0.24-0.96 mmol.L-1) induced apoptosis of trabecular meshwork cells in a dose and time-dependent manner. Before 0.48 mmol.L-1 dexamethasone-treatment, 1.84 mmol.L-1 of pilocarpine or 2.74 mmol.L-1 of carbachol added could significantly reduce apoptotic percentage. CONCLUSION: Muscarinic receptor agonists can protect cultured bovine trabecular meshwork cells against apoptosis induced by dexamethasone.

Animals↗
PubMed2006

[Relationship between glucocorticoid receptors in the peripheral blood lymphocytes and trabecular meshwork and glucocorticoid induced glaucoma].

OBJECTIVE: To measure the number of glucocorticoid receptors (GR) in the trabecular meshwork and peripheral blood lymphocytes of rabbits, and to explore their relationship with steroid-induced glaucoma. METHODS: Steroid-induced glaucoma model was induced by subconjunctival injection of 0.5 mg dexamethasone in the right eyes every two days for a month. Before the injection, GR concentration was measured in peripheral blood lymphocytes and trabecular meshwork of rabbits using the radio-ligand binding assay. GR concentration was measured again 30 days after the injection. The data was analyzed with SPSS software. RESULTS: The GR concentration in the peripheral blood lymphocytes and the trabecular meshwork of rabbits was (3642 +/- 947) site/cell and (2437.85 +/- 733.93) dmp/mg, respectively. The expression level in lymphocytes was significantly correlated with that in the trabecular (r = 0.862, P < 0.01). After treated with dexamethasone, the intraocular pressure of rabbits increased significantly, and the GR concentration in peripheral blood lymphocytes decreased significantly. Elevating level of IOP correlated positively with the primary and decreasing level of GR (r = 0.78, 0.79, P < 0.01). CONCLUSIONS: GR concentration in the peripheral blood lymphocytes of rabbits can reflect directly the GR number in the trabecular meshwork. There may be a close relationship between the GR number in peripheral blood lymphocytes and steroid-induced glaucoma.

Animals↗
PubMed1996

[A study of 5-fluorouracil on bovine trabecular meshwork cells in vitro].

OBJECTIVE: To determine whether the clinical use of 5-fluorouracil (5-FU) may have any toxic effects on trabecular meshwork cells. METHODS: Bovine trabecular meshwork (BTM) cells were cultured in vitro. The effects of 5-FU on BTM cells concerning cellular morphology, ultrastructure, vitality and phagocytosis were observed. RESULT: The safe dosage of 5-FU on BTM cell was 1 x 10-6g.ml-1. CONCLUSION: Based on the pharmacokinetic data in the rabbit anterior chamber, it is suggested that the 5-FU dosage of conventional use cause no injury to human trabecular meshwork cells.

Animals↗
PubMed2000

Functional identification of phosphodiesterase activity in human trabecular meshwork cells.

The phosphodiesterases (PDE) activity in human trabecular meshwork cells (HTM-3) was investigated in this study in order to better understand the signal transduction pathways in the conventional outflow tract of the eye. Agonists (isoproterenol or nitroprusside) were used to stimulate adenylyl cyclase and guanylyl cyclase, respectively, in the absence and presence of nonselective IBMX or PDE5 specific inhibitors E4021 (1). The subcellular distribution of cAMP and cGMP PDEs was determined directly by PDE enzyme assays using HTM-3 cells. Levels of cyclic nucleotides were measured in the same cells by radioimmunoassay (RIA). Isoproterenol alone elevated cAMP levels, and this response was enhanced by IBMX. Nitroprusside alone caused no increase in basal cGMP levels but, in the presence of E4021, nitroprusside produced significant, dose-related elevation of cGMP levels. Subcellular distribution experiments indicated that the greatest activity for PDEs resided in the supernatant fraction. In conclusion, HTM-3 cells contain PDEs that degrade both cyclic nucleotides. The PDE activities reside predominantly in the supernatant, but the PDE activity for degrading cGMP is more pronounced. Moreover, results with E4021 suggest that PDE5 activity could play a critical role in modulating cGMP-related activity in the trabecular meshwork.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Collagen fibrils as skeletal frame in monkey trabecular meshwork.

In an attempt to identify the characteristic skeletal frame of the trabecular meshwork, the three-dimensional architecture of collagen fibrillar bundles (collagen bundles) was studied by applying the NaOH cell-maceration method to the anterior segment of cynomolgus monkey eyes. Collagen bundles in the trabecular meshwork were found to be continuous with thinner collagen lamellae in the peripheral cornea and with the collagen fibril plexus in the ciliary body. The collagen core in the uveal cord was columnar in shape and was arranged parallel to the long axis. Collagen bundles were arranged as the layered network forming the fundamental framework of the trabecular meshwork. Most collagen bundles of the corneoscleral sheet were arranged circularly, parallel to the circumference of the limbus, and numerous slender bundles were observed side by side, forming the flat and membranous configuration of the sheet. The endothelial meshwork consisted of a network of fine and sparse collagen fibrils forming extracellular spaces and intercommunicating openings. The inner wall of the canal of Schlemm was seen as a netlike surface of sparse collagen fibrils with variously sized circular openings. The openings suggested the possibility that development of giant vacuoles corresponds to the circular openings under the inner endothelial cell lining.

Animals↗
PubMedDate not supplied

Glycosaminoglycans in human trabecular meshwork: age-related changes.

Glycosaminoglycans play a central role in maintaining the normal outflow resistance in the human trabecular meshwork. We evaluated the possible morphological, histochemical and morphometrical age-related changes in glycosaminoglycans of the trabecular meshwork. Small human samples were drawn from 24 eyes after exitus from young and old humans. Samples were harvested from the anterior chamber of the eye, without any aesthetic damage for the face. They were divided into three fragments, each used for morphological, histochemical and ultrastructural staining. Quantitative analysis of images was performed to evaluate morphometrical data that were statistically analysed. Our findings demonstrate the following age-related changes: (1) deposition of fibrous granular material in the trabecular meshwork; (2) increased electron density of the structures; (3) strong decrease in the hyaluronic acid content, and (4) increase in sulphated proteoglycans. Glycosaminoglycans of human trabecular meshwork undergo age-related changes, as demonstrated by our morphological, histochemical and morphometrical results.

Adult↗
PubMed1992

Effects of elastase on cultured human trabecular meshwork.

We evaluated the effect of elastase, a proteolytic enzyme, on the endothelial meshwork of cultured human trabecular meshwork using a solid agar method. The tissues were obtained from 3 postmortem eyes, aged 64, 71 and 77 years. Elastase was added to the culture medium for 24 h at a concentration of 1 x 10(-1)-10(-4) mg/ml. The cultured specimens were then processed for transmission electron microscopy. We evaluated the electron micrographs to determine the percent area occupied by the cells and the extracellular materials and by the empty space in the endothelial meshwork using computer-assisted morphometry. A statistically significant decrease in extracellular materials with intact trabecular cells was confirmed 24 h following the administration of elastase at the concentration of 1 x 10(-1)-10(-3) mg/ml.

Aged↗
PubMed1994

Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide.

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.

Amino Acid Oxidoreductases↗
PubMed2001

Toxic effects of mitomycin-C on cultured ciliary process cells and trabecular meshwork cells.

Mitomycin-C has recently become an adjunct medication for inhibition of fibroblast proliferation in glaucoma filtering procedures. Prolonged postoperative ocular hypotony has been a frequent complication of trabeculectomy with mitomycin-C. In order to characterize the hypotony mechanism, we compared the toxic effects of mitomycin-C on cultured rabbit ciliary process cells and trabecular meshwork cells. The results indicate that mitomycin-C has a more marked effect on ciliary process cells on 3H-thymidine uptake than on trabecular meshwork cells at concentrations ranging from 10(-1) to 10(-5) mg/ml after 3-, 5- and 60-min treatment, respectively. The living cells after mitomycin-C treatment were estimated with MTT assay that was converted tetrazolium dye of living cells only into insoluble purple formazan crystals within mitochondria. In the presence of mitomycin-C for 3, 5, and 60 min, the cellular MTT values in ciliary process cells were more decreased than in trabecular meshwork cells. Depolarization of the trabecular meshwork cells with 50 mM KCl led to an increase in intracellular calcium concentration, whereas application of mitomycin-C at 10(-3) mg/ml resulted in decrease of KCl-induced intracellular calcium increase. Mitomycin-C (10(-3) mg/ml) decreased cAMP concentration in ciliary process cells following 3- and 5-min treatment; however, it did not significantly affect the cellular cAMP concentration after only a 1-min exposure. Mitomycin-induced marked ladder pattern of DNA fragmentation was observed in ciliary process tissues after treatment with 10(-1) mg/ml of mitomycin-C for 3 and 5 min. However, the DNA pattern in trabecular meshwork tissues was not obviously affected by mitomycin-C. These findings from our results indicate that mitomycin-induced ocular hypotony may result from damage to both ciliary process and trabecular meshwork tissues.

Animals↗
PubMed2006

Noladin ether acts on trabecular meshwork cannabinoid (CB1) receptors to enhance aqueous humor outflow facility.

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 antibodies was used to detect focal adhesions. RESULTS: Within 1 hour after adding 3, 30, or 300 nM of noladin ether, the aqueous humor outflow facility increased concentration dependently. The effect of 30 nM of noladin ether was completely blocked by SR141716A, a selective CB1 antagonist. Positive signals were detected on cultured porcine trabecular meshwork cells with an anti-CB1 antibody in immunofluorescence microscopy and Western blot studies. Treatment of trabecular meshwork cells with 30 nM of noladin ether activated p42/44 MAP kinase, whereas pretreatment with SR141716A blocked the p42/44 MAP kinase-activating effects of noladin ether. In addition, the enhancement of outflow facility induced by noladin ether was blocked by pretreatment of porcine anterior segments with PD98059, an inhibitor of p42/44 MAP kinase pathway. Furthermore, noladin ether treatment caused rounding of trabecular meshwork cells, and there was a decrease of actin stress fibers, as well as a decrease in focal adhesions. These noladin ether-induced morphologic changes were also blocked by SR141716A and PD98059. CONCLUSIONS: The results demonstrate for the first time that administration of noladin ether, an endocannabinoid agonist selective for the CB1 receptor, increases aqueous humor outflow facility. The data also show that noladin ether-induced enhancement of outflow facility is mediated through the trabecular meshwork CB1 receptor, with an involvement of p42/44 MAP kinase signaling pathway and changes in actin cytoskeletons.

Actins↗
PubMed1998

Introduction of DNA into the rat and primate trabecular meshwork by fusogenic liposomes.

PURPOSE: To evaluate the feasibility of introducing exogenous genes and phosphorothioate oligonucleotides into the anterior chamber tissues of rats and monkeys using the authors' fusogenic liposomes. METHODS: Hemagglutinating virus of Japan liposomes containing LacZ DNA-high-mobility group 1 complexes or fluorescein isothiocyanate (FITC)-labeled phosphorothioate oligonucleotides were prepared and injected into the anterior chambers of rats (3 microliters) and rhesus monkeys (30 microliters). The expression of LacZ DNA was visualized histochemically by beta-Galactosidase assay and was followed for as long as 60 days in rats and 30 days in monkeys. FITC-labeled phosphorothioate oligonucleotides were observed by fluorescence microscopy for as long as 14 days in rats and 7 days in monkeys. RESULTS: Injection of LacZ DNA-high-mobility group 1 complexes encapsulated in hemagglutinating virus of Japan liposomes resulted in blue staining in the trabecular meshwork and iris-ciliary body of rats and selectively in the trabecular meshwork of monkeys at the concentrations used. This LacZ expression lasted for as long as 14 days after injection in both animals. Phosphorothioate oligonucleotides (3 microM) also were introduced into the rat trabecular meshwork and iris-ciliary body and into the primate trabecular meshwork when encapsulated in hemagglutinating virus of Japan liposomes, although the injection of naked FITC-labeled phosphorothioate oligonucleotides at the same concentration resulted in little fluorescence in any anterior chamber tissue. CONCLUSIONS: This study shows that the use of hemagglutinating virus of Japan liposomes can transfer LacZ DNA and phosphorothioate oligonucleotides to adult rat and primate trabecular meshwork. This system may enable progress in glaucoma research and in the development of nonviral somatic gene therapy of the trabecular meshwork to treat glaucoma.

Animals↗